{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:47:33Z","timestamp":1790844453062,"version":"4.1.0"},"reference-count":214,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T00:00:00Z","timestamp":1516752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU SysteMTb","award":["HEALTH-F4-2010-241587"],"award-info":[{"award-number":["HEALTH-F4-2010-241587"]}]},{"name":"EU Horizon 2020, MycoSynVac","award":["634942"],"award-info":[{"award-number":["634942"]}]},{"name":"EU FP7 programme, INFECT","award":["305340"],"award-info":[{"award-number":["305340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis remains one of the deadliest diseases. Emergence of drug-resistant and multidrug-resistant M. tuberculosis strains makes treating tuberculosis increasingly challenging. In order to develop novel intervention strategies, detailed understanding of the molecular mechanisms behind the success of this pathogen is required. Here, we review recent literature to provide a systems level overview of the molecular and cellular components involved in divalent metal homeostasis and their role in regulating the three main virulence strategies of M. tuberculosis: immune modulation, dormancy and phagosomal rupture. We provide a visual and modular overview of these components and their regulation. Our analysis identified a single regulatory cascade for these three virulence strategies that respond to limited availability of divalent metals in the phagosome.<\/jats:p>","DOI":"10.3390\/ijms19020347","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T09:47:36Z","timestamp":1516787256000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Regulation of Three Virulence Strategies of Mycobacterium tuberculosis: A Success Story"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-5334","authenticated-orcid":false,"given":"Niels","family":"Zondervan","sequence":"first","affiliation":[{"name":"Laboratory of Systems and Synthetic Biology, Wageningen University &amp; Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Van Dam","sequence":"additional","affiliation":[{"name":"Laboratory of Systems and Synthetic Biology, Wageningen University &amp; Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4346-6084","authenticated-orcid":false,"given":"Peter","family":"Schaap","sequence":"additional","affiliation":[{"name":"Laboratory of Systems and Synthetic Biology, Wageningen University &amp; Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor","family":"Martins dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Systems and Synthetic Biology, Wageningen University &amp; Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands"},{"name":"LifeGlimmer GmbH, Markelstrasse 38, 12163 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-146X","authenticated-orcid":false,"given":"Maria","family":"Suarez-Diez","sequence":"additional","affiliation":[{"name":"Laboratory of Systems and Synthetic Biology, Wageningen University &amp; Research, Stippeneng 4, 6708 WE Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2017). Global Tuberculosis Report 2017, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1111\/j.1742-4658.2010.07666.x","article-title":"Rajni Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv","volume":"277","author":"Meena","year":"2010","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1574-6976.2012.00331.x","article-title":"Mycobacterium tuberculosis: Success through dormancy","volume":"36","author":"Gengenbacher","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1073\/pnas.1620133114","article-title":"Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions","volume":"114","author":"Conrad","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12703\/P7-29","article-title":"Duality of lipid mediators in host response against Mycobacterium tuberculosis: Good cop, bad cop","volume":"7","author":"Dietzold","year":"2015","journal-title":"F1000Prime Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2013.00098","article-title":"Modeling the Mycobacterium tuberculosis granuloma\u2014The critical battlefield in host immunity and disease","volume":"4","author":"Guirado","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Silva Miranda, M., Breiman, A., Allain, S., Deknuydt, F., and Altare, F. (2012). The tuberculous granuloma: An unsuccessful host defence mechanism providing a safety shelter for the bacteria?. Clin. Dev. Immunol., 2012.","DOI":"10.1155\/2012\/139127"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.tube.2003.08.003","article-title":"Tuberculosis persistence, latency, and drug tolerance","volume":"84","author":"Gomez","year":"2004","journal-title":"Tuberculosis"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kapoor, N., Pawar, S., Sirakova, T.D., Deb, C., Warren, W.L., and Kolattukudy, P.E. (2013). Human granuloma in vitro model, for TB dormancy and resuscitation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053657"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1462-5822.2009.01424.x","article-title":"Penitentiary or penthouse condo: The tuberculous granuloma from the microbe\u2019s point of view","volume":"12","author":"Paige","year":"2010","journal-title":"Cell. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shaler, C.R., Horvath, C.N., Jeyanathan, M., and Xing, Z. (2013). Within the Enemy\u2019s Camp: Contribution of the granuloma to the dissemination, persistence and transmission of Mycobacterium tuberculosis. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00030"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/ni.1781","article-title":"Foamy macrophages and the progression of the human tuberculosis granuloma","volume":"10","author":"Russell","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Simeone, R., Bobard, A., Lippmann, J., Bitter, W., Majlessi, L., Brosch, R., and Enninga, J. (2012). Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002507"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sani, M., Houben, E.N.G., Geurtsen, J., Pierson, J., de Punder, K., van Zon, M., Wever, B., Piersma, S.R., Jim\u00e9nez, C.R., and Daff\u00e9, M. (2010). Direct visualization by Cryo-EM of the mycobacterial capsular layer: A labile structure containing ESX-1-secreted proteins. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000794"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.3390\/ijms9081548","article-title":"The metal-dependent regulators FurA and FurB from Mycobacterium tuberculosis","volume":"9","author":"Lucarelli","year":"2008","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/mmi.13034","article-title":"Manganese homeostasis and utilization in pathogenic bacteria","volume":"97","author":"Juttukonda","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1182\/blood-2003-02-0425","article-title":"Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane","volume":"102","author":"Forbes","year":"2003","journal-title":"Blood"},{"key":"ref_18","first-page":"646","article-title":"Nutritional immunity: Transition metals at the pathogen-host interface","volume":"10","author":"Indriate","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/mmi.12441","article-title":"IdeR is required for iron homeostasis and virulence in Mycobacterium tuberculosis","volume":"91","author":"Pandey","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev.micro.60.080805.142149","article-title":"Manganese transport and the role of manganese in virulence","volume":"60","author":"Maguire","year":"2006","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35141","DOI":"10.1074\/jbc.M104108200","article-title":"Eukaryotic-like adenylyl cyclases in Mycobacterium tuberculosis H37Rv: Cloning and characterization","volume":"276","author":"Reddy","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1128\/JB.01190-06","article-title":"Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon","volume":"189","author":"Maciag","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e01092-17","DOI":"10.1128\/mBio.01092-17","article-title":"The capacity of Mycobacterium tuberculosis to survive iron starvation might enable it to persist in iron-deprived microenvironments of human granulomas","volume":"8","author":"Kurthkoti","year":"2017","journal-title":"mBio"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lin, H., Andersen, G.R., and Yatime, L. (2016). Crystal structure of human S100A8 in complex with zinc and calcium. BMC Struct. Biol., 16.","DOI":"10.1186\/s12900-016-0058-4"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49727","DOI":"10.1074\/jbc.M209768200","article-title":"Intraphagosomal Mycobacterium tuberculosis acquires iron from both extracellular transferrin and intracellular iron pools. Impact of interferon-gamma and hemochromatosis","volume":"277","author":"Olakanmi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Blanchette, C.D., Woo, Y.-H., Thomas, C., Shen, N., Sulchek, T.A., and Hiddessen, A.L. (2009). Decoupling internalization, acidification and phagosomal-endosomal\/lysosomal fusion during phagocytosis of InlA coated beads in epithelial cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006056"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0966-842X(01)02098-4","article-title":"Divalent-metal transport by NRAMP proteins at the interface of host-pathogen interactions","volume":"9","author":"Forbes","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1128\/IAI.72.4.2022-2028.2004","article-title":"The nature of extracellular iron influences iron acquisition by Mycobacterium tuberculosis residing within human macrophages","volume":"72","author":"Olakanmi","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1084\/jem.192.9.1237","article-title":"Natural resistance to intracellular infections: Natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane","volume":"192","author":"Jabado","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5105","DOI":"10.1073\/pnas.93.10.5105","article-title":"A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria","volume":"93","author":"Supek","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1242\/jcs.116210","article-title":"The Nramp (Slc11) proteins regulate development, resistance to pathogenic bacteria and iron homeostasis in Dictyostelium discoideum","volume":"126","author":"Peracino","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.4049\/jimmunol.174.3.1491","article-title":"Elemental analysis of Mycobacterium avium-, Mycobacterium tuberculosis-, and Mycobacterium smegmatis-containing phagosomes indicates pathogen-induced microenvironments within the host cell\u2019s endosomal system","volume":"174","author":"Wagner","year":"2013","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1111\/mmi.13207","article-title":"MntR(Rv2788): A transcriptional regulator that controls manganese homeostasis in Mycobacterium tuberculosis","volume":"98","author":"Pandey","year":"2015","journal-title":"Mol. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1006\/jmbi.1998.2339","article-title":"Crystal structure of the iron-dependent regulator (IdeR) from Mycobacterium tuberculosis shows both metal binding sites fully occupied","volume":"285","author":"Pohl","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.jmb.2006.10.080","article-title":"The conformations of the manganese transport regulator of Bacillus subtilis in its metal-free state","volume":"365","author":"Dewitt","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nchembio717","article-title":"Mycobactin-mediated iron acquisition within macrophages","volume":"1","author":"Luo","year":"2005","journal-title":"Nat. Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1128\/JB.00088-12","article-title":"Analyses of MbtB, MbtE, and MbtF suggest revisions to the Mycobactin biosynthesis pathway in Mycobacterium tuberculosis","volume":"194","author":"McMahon","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms5730","article-title":"Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin","volume":"5","author":"Boradia","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1073\/pnas.1109958109","article-title":"Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis","volume":"109","author":"Madigan","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rohde, K.H., Veiga, D.F.T., Caldwell, S., Bal\u00e1zsi, G., and Russell, D.G. (2012). Linking the transcriptional profiles and the physiological states of Mycobacterium tuberculosis during an extended intracellular infection. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002769"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.freeradbiomed.2015.03.008","article-title":"Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide","volume":"84","author":"Tyagi","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1128\/IAI.70.7.3371-3381.2002","article-title":"ideR, an essential gene in Mycobacterium tuberculosis: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response","volume":"70","author":"Rodriguez","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vilch\u00e8ze, C., Hartman, T., Weinrick, B., and William, R.J. (2013). Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction. Nat. Commun., 4.","DOI":"10.1038\/ncomms2898"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1128\/CMR.6.2.137","article-title":"Role of iron in regulation of virulence genes","volume":"6","author":"Litwin","year":"1993","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nrmicro1046","article-title":"Iron and microbial infection","volume":"2","author":"Schaible","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1089\/ars.2008.2296","article-title":"Iron-based redox switches in biology","volume":"11","author":"Outten","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18792","DOI":"10.1073\/pnas.0900589106","article-title":"Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition","volume":"106","author":"Siegrist","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.1128\/JB.00756-09","article-title":"Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: Essentiality and rescue by iron and zinc","volume":"191","author":"Serafini","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Farhana, A., Kumar, S., Rathore, S.S., Ghosh, P.C., Ehtesham, N.Z., Tyagi, A.K., and Hasnain, S.E. (2008). Mechanistic insights into a novel exporter-importer system of Mycobacterium tuberculosis unravel its role in trafficking of iron. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002087"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1046\/j.1365-2958.2001.02684.x","article-title":"The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages","volume":"42","author":"Gold","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1046\/j.1365-2958.2003.03384.x","article-title":"Mechanisms of iron regulation in mycobacteria: Role in physiology and virulence","volume":"47","author":"Rodriguez","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_52","first-page":"418","article-title":"The mycobacterial iron dependent regulator IdeR induces ferritin (bfrB) by alleviating Lsr2 repression","volume":"528","author":"Oldridge","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18741","DOI":"10.1073\/pnas.1014494107","article-title":"Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis","volume":"107","author":"Fu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1073\/pnas.0810126106","article-title":"The multifunctional histone-like protein Lsr2 protects mycobacteria against reactive oxygen intermediates","volume":"106","author":"Colangeli","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1371\/journal.ppat.0030087","article-title":"Transcriptional regulation of multi-drug tolerance and antibiotic-induced responses by the histone-like protein Lsr2 in M. tuberculosis","volume":"3","author":"Colangeli","year":"2007","journal-title":"PLoS Pathog."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0169545","article-title":"Differential roles of iron storage proteins in maintaining the iron homeostasis in Mycobacterium tuberculosis","volume":"12","author":"Khare","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1073\/pnas.1311402111","article-title":"Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling","volume":"111","author":"Jones","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1128\/JB.01483-13","article-title":"Iron-regulated protein HupB of Mycobacterium tuberculosis positively regulates siderophore biosynthesis and is essential for growth in macrophages","volume":"196","author":"Pandey","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1128\/JB.00359-16","article-title":"Iron homeostasis in Mycobacterium tuberculosis: Mechanistic insights into siderophore-mediated iron uptake","volume":"198","author":"Sritharan","year":"2016","journal-title":"Bacteriology"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gonzalo-Asensio, J., Mostowy, S., Harders-Westerveen, J., Huygen, K., Hern\u00e1ndez-Pando, R., Thole, J., Behr, M., Gicquel, B., and Mart\u00edn, C. (2008). PhoP: A missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003496"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5328","DOI":"10.1016\/j.febslet.2006.09.004","article-title":"Transcriptional autoregulation by Mycobacterium tuberculosis PhoP involves recognition of novel direct repeat sequences in the regulatory region of the promoter","volume":"580","author":"Gupta","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7068","DOI":"10.1128\/JB.00712-08","article-title":"The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv","volume":"190","author":"Soto","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12844","DOI":"10.1073\/pnas.96.22.12844","article-title":"Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor","volume":"96","author":"Manabe","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1128\/JB.00026-07","article-title":"Iron-dependent RNA-binding activity of Mycobacterium tuberculosis aconitase","volume":"189","author":"Banerjee","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1128\/JB.01690-12","article-title":"Two roles for aconitase in the regulation of tricarboxylic acid branch gene expression in Bacillus subtilis","volume":"195","author":"Pechter","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.chom.2007.09.006","article-title":"Mycobacterium tuberculosis invasion of macrophages: Linking bacterial gene expression to environmental cues","volume":"2","author":"Rohde","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/mmi.13449","article-title":"\u03c3E-dependent activation of RbpA controls transcription of the furA-katG operon in response to oxidative stress in mycobacteria","volume":"102","author":"Hu","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12013-012-9348-z","article-title":"The function and regulatory network of WhiB and WhiB-like protein from comparative genomics and systems biology perspectives","volume":"63","author":"Zheng","year":"2012","journal-title":"Cell Biochem. Biophys."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1128\/AAC.02191-12","article-title":"Aminoglycoside cross-resistance in Mycobacterium tuberculosis due to mutations in the 5\u2032 untranslated region of whiB7","volume":"57","author":"Reeves","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1099\/mic.0.2006\/002642-0","article-title":"Expression, production and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion","volume":"153","author":"Samuel","year":"2007","journal-title":"Microbiology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.neuint.2012.12.006","article-title":"Metals, oxidative stress and neurodegeneration: A focus on iron, manganese and mercury","volume":"62","author":"Farina","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1099\/mic.0.045807-0","article-title":"Yersinia pseudotuberculosis mntH functions in intracellular manganese accumulation, which is essential for virulence and survival in cells expressing functional Nramp1","volume":"157","author":"Champion","year":"2011","journal-title":"Microbiology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1017\/S1462399411002079","article-title":"Redox homeostasis in mycobacteria: The key to tuberculosis control?","volume":"13","author":"Kumar","year":"2011","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.gene.2007.10.017","article-title":"Genome scale portrait of cAMP-receptor protein (CRP) regulons in mycobacteria points to their role in pathogenesis","volume":"407","author":"Akhter","year":"2008","journal-title":"Gene"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"fnv183","DOI":"10.1093\/femsle\/fnv183","article-title":"Revisiting bacterial cyclic nucleotide phosphodiesterases: Cyclic AMP hydrolysis and beyond","volume":"362","author":"Matange","year":"2015","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3824","DOI":"10.1128\/JB.00138-08","article-title":"Cyclic AMP in mycobacteria: Characterization and functional role of the Rv1647 ortholog in Mycobacterium smegmatis","volume":"190","author":"Dass","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1462-5822.2010.01562.x","article-title":"Cyclic AMP signalling in mycobacteria: Redirecting the conversation with a common currency","volume":"13","author":"Bai","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ijmm.2006.07.001","article-title":"Characterization of a Mycobacterium tuberculosis mutant deficient in pH-sensing adenylate cyclase Rv1264","volume":"296","author":"Dittrich","year":"2006","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nature08123","article-title":"Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase","volume":"460","author":"Agarwal","year":"2009","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Daniel, J., Abraham, L., Martin, A., Pablo, X., and Reyes, S. (2017). Rv2477c is an antibiotic-sensitive manganese-dependent ABC-F ATPase in Mycobacterium tuberculosis. Biochem. Biophys. Res. Commun., 1\u20136.","DOI":"10.1016\/j.bbrc.2017.10.168"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s12011-009-8406-x","article-title":"Salmonella-macrophage interactions upon manganese supplementation","volume":"133","author":"Rishi","year":"2010","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.chom.2016.05.005","article-title":"Salmonella mitigates oxidative stress and thrives in the inflamed gut by evading calprotectin-mediated article salmonella mitigates oxidative stress and thrives in the inflamed gut by evading calprotectin-mediated manganese sequestration","volume":"19","author":"Lam","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1084\/jem.190.5.717","article-title":"Mycobacterium tuberculosis expresses a novel pH-dependent divalent cation transporter belonging to the Nramp family","volume":"190","author":"Agranoff","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1128\/JB.01067-12","article-title":"MprAB regulates the espA operon in Mycobacterium tuberculosis and modulates ESX-1 function and host cytokine response","volume":"195","author":"Pang","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1016\/j.celrep.2016.07.080","article-title":"Mycobacterial WhiB6 differentially regulates ESX-1 and the dos regulon to modulate granuloma formation and virulence in zebrafish","volume":"16","author":"Chen","year":"2016","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1128\/JB.01318-08","article-title":"Three Mycobacterium tuberculosis Rel Toxin-antitoxin modules inhibit mycobacterial growth and are expressed in infected human macrophages","volume":"191","author":"Korch","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1111\/febs.12815","article-title":"Characterization of the interaction between a SirR family transcriptional factor of Mycobacterium tuberculosis, encoded by Rv2788, and a pair of toxin-antitoxin proteins RelJ\/K, encoded by Rv3357 and Rv3358","volume":"281","author":"Yang","year":"2014","journal-title":"FEBS J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8564","DOI":"10.1093\/nar\/gkx489","article-title":"Functional details of the Mycobacterium tuberculosis VapBC26 toxin-antitoxin system based on a structural study: Insights into unique binding and antibiotic peptides","volume":"45","author":"Kang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7624","DOI":"10.1093\/nar\/gkv689","article-title":"Structural and functional studies of the Mycobacterium tuberculosis VapBC30 toxin-antitoxin system: Implications for the design of novel antimicrobial peptides","volume":"43","author":"Lee","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0078351","article-title":"The ESX-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis","volume":"8","author":"Serafini","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1128\/JB.01064-13","article-title":"The MprB extracytoplasmic domain negatively regulates activation of the Mycobacterium tuberculosis MprAB two-component system","volume":"196","author":"Bretl","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"29993","DOI":"10.1074\/jbc.M111.248732","article-title":"Solution structure of the Mycobacterium tuberculosis EsxG\u00b7EsxH complex: Functional implications and comparisons with other M. tuberculosis Esx family complexes","volume":"286","author":"Ilghari","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6116","DOI":"10.1128\/JB.00802-09","article-title":"Contributions of zur-controlled ribosomal proteins to growth under zinc starvation conditions","volume":"191","author":"Gabriel","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Houben, E.N.G., Korotkov, K.V., and Bitter, W. (2013). Take five\u2014Type VII secretion systems of mycobacteria. Biochim. Biophys. Acta.","DOI":"10.1016\/j.bbamcr.2013.11.003"},{"key":"ref_95","unstructured":"Newton-Foot, M. (2010). The Mycobacterium tuberculosis ESX-3 Secretion System Interactome. [Master\u2019s Thesis, University of Stellenbsoch]."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mib.2008.11.003","article-title":"ESX\/type VII secretion systems and their role in host-pathogen interaction","volume":"12","author":"Simeone","year":"2009","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Mehra, A., Zahra, A., Thompson, V., Sirisaengtaksin, N., Wells, A., Porto, M., K\u00f6ster, S., Penberthy, K., Kubota, Y., and Dricot, A. (2013). Mycobacterium tuberculosis Type VII Secreted Effector EsxH Targets Host ESCRT to Impair Trafficking. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003734"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"E348","DOI":"10.1073\/pnas.1523321113","article-title":"Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence","volume":"113","author":"Tufariello","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","first-page":"1","article-title":"Integration of heterogeneous molecular networks to unravel gene-regulation in Mycobacterium tuberculosis","volume":"8","author":"Schaap","year":"2014","journal-title":"BMC Med. Genom."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Tiwari, B.M., Kannan, N., Vemu, L., and Raghunand, T.R. (2012). The Mycobacterium tuberculosis PE proteins Rv0285 and Rv1386 modulate innate immunity and mediate bacillary survival in macrophages. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051686"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Li, W., Zhao, Q., Deng, W., Chen, T., Liu, M., and Xie, J. (2014). Mycobacterium tuberculosis Rv3402c Enhances mycobacterial survival within macrophages and modulates the host pro-inflammatory cytokines production via NF-Kappa B\/ERK\/p38 signaling. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094418"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1099\/jmm.0.026047-0","article-title":"Expression of the Mycobacterium tuberculosis PPE37 protein in Mycobacterium smegmatis induces low tumour necrosis factor alpha and interleukin 6 production in murine macrophages","volume":"60","author":"Daim","year":"2011","journal-title":"J. Med. Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4675","DOI":"10.1021\/acs.biochem.6b00289","article-title":"The PE_PGRS proteins of Mycobacterium tuberculosis are Ca2+ binding mediators of host\u2013pathogen interaction","volume":"55","author":"Yeruva","year":"2016","journal-title":"Biochemistry"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2017.00068","article-title":"PPE38 protein of Mycobacterium tuberculosis inhibits macrophage MHC class I expression and dampens CD8+ T cell responses","volume":"7","author":"Meng","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1128\/IAI.05249-11","article-title":"PPE38 modulates the innate immune response and is required for Mycobacterium marinum virulence","volume":"80","author":"Dong","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.4049\/jimmunol.1202722","article-title":"IL-10 inhibits mature fibrotic granuloma formation during Mycobacterium tuberculosis infection","volume":"190","author":"Cyktor","year":"2013","journal-title":"J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.4049\/jimmunol.1103038","article-title":"Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPAR\u03b3 and TR4 for survival","volume":"188","author":"Mahajan","year":"2012","journal-title":"J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1096\/fj.09-148155","article-title":"Interleukin-10 overexpression in macrophages suppresses atherosclerosis in hyperlipidemic mice","volume":"24","author":"Han","year":"2010","journal-title":"FASEB J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1128\/JB.01090-13","article-title":"Role for Mycobacterium tuberculosis membrane vesicles in iron acquisition","volume":"196","author":"Weinrick","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1600-0854.2011.01165.x","article-title":"Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes","volume":"12","author":"Seto","year":"2011","journal-title":"Traffic"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"13326","DOI":"10.1074\/jbc.272.20.13326","article-title":"Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7","volume":"272","author":"Via","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"19371","DOI":"10.1073\/pnas.1109201108","article-title":"Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification","volume":"108","author":"Wong","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1242\/jcs.03091","article-title":"cAMP synthesis and degradation by phagosomes regulate actin assembly and fusion events: Consequences for mycobacteria","volume":"119","author":"Kalamidas","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.imbio.2011.07.008","article-title":"Mycobacterium tuberculosis: Immune evasion, latency and reactivation","volume":"217","author":"Gupta","year":"2012","journal-title":"Immunobiology"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Thi, E.P., Lambertz, U., and Reiner, N.E. (2012). Sleeping with the enemy: How intracellular pathogens cope with a macrophage lifestyle. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002551"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1146\/annurev-pharmtox-061008-103123","article-title":"Mycobacterial subversion of chemotherapeutic reagents and host defense tactics: Challenges in tuberculosis drug development","volume":"49","author":"Nguyen","year":"2009","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1742-4658.2008.06755.x","article-title":"Studies on structural and functional divergence among seven WhiB proteins of Mycobacterium tuberculosis H37Rv","volume":"276","author":"Alam","year":"2009","journal-title":"FEBS J."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Larsson, C., Luna, B., Ammerman, N.C., Maiga, M., Agarwal, N., and Bishai, W.R. (2012). Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037516"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1042\/BJ20101440","article-title":"Europe PMC Funders Group Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide sensitive iron-sulphur cluster","volume":"432","author":"Smith","year":"2010","journal-title":"Biochem. J."},{"key":"ref_120","unstructured":"Ranganathan, S., Bai, G., Lyubetskaya, A., Gwendowlyn, S., Galagan, E., and Mcdonough, K.A. (2002). Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon. Nucleic Acids Res., 1\u201354."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/j.1365-2958.2012.08165.x","article-title":"Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo","volume":"85","author":"Chawla","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3132","DOI":"10.1128\/IAI.06328-11","article-title":"WhiB5, a transcriptional regulator that contributes to Mycobacterium tuberculosis virulence and reactivation","volume":"80","author":"Casonato","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"11562","DOI":"10.1073\/pnas.0700490104","article-title":"Mycobacterium tuberculosis WhiB3 responds to O2 and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival","volume":"104","author":"Singh","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.tube.2012.03.001","article-title":"Mycobacterium tuberculosis WhiB1 represses transcription of the essential chaperonin GroEL2","volume":"92","author":"Stapleton","year":"2012","journal-title":"Tuberculosis"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1365-2958.2011.07601.x","article-title":"aprABC: A Mycobacterium tuberculosis complex-specific locus that modulates pH-driven adaptation to the macrophage phagosome","volume":"80","author":"Abramovitch","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Singh, A., Crossman, D.K., Mai, D., Guidry, L., Voskuil, M.I., Renfrow, M.B., and Steyn, A.J.C. (2009). Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000545"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-014-1197-2","article-title":"Comprehensive insights into transcriptional adaptation of intracellular mycobacteria by microbe-enriched dual RNA sequencing","volume":"16","author":"Rienksma","year":"2015","journal-title":"BMC Genom."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mSystems.00057-17","article-title":"Integration of metabolomics and transcriptomics reveals a complex diet of mycobacterium tuberculosis during early macrophage infection","volume":"2","author":"Zimmermann","year":"2017","journal-title":"MSystems"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature12337","article-title":"The Mycobacterium tuberculosis regulatory network and hypoxia","volume":"499","author":"Galagan","year":"2013","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1089\/ars.2011.4341","article-title":"Mycobacterium tuberculosis WhiB3: A novel iron-sulfur cluster protein that regulates redox homeostasis and virulence","volume":"16","author":"Saini","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1128\/JB.187.8.2681-2692.2005","article-title":"Identification of cyclic AMP-regulated genes in Mycobacterium tuberculosis complex bacteria under low-oxygen conditions identification of cyclic AMP-regulated genes in Mycobacterium tuberculosis complex bacteria under low-oxygen conditions","volume":"187","author":"Gazdik","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_132","first-page":"481","article-title":"Mycobacterium tuberculosis Cpn60. 2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin","volume":"2","author":"Joseph","year":"2017","journal-title":"Biol. Open"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Naffin-Olivos, J.L., Georgieva, M., Goldfarb, N., Madan-Lala, R., Dong, L., Bizzell, E., Valinetz, E., Brandt, G.S., Yu, S., and Shabashvili, D.E. (2014). Mycobacterium tuberculosis Hip1 modulates macrophage responses through proteolysis of GroEL2. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004132"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/viru.22329","article-title":"Virulence factors of the Mycobacterium tuberculosis complex","volume":"4","author":"Forrellad","year":"2013","journal-title":"Virulence"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/srep01328","article-title":"Characterizing virulence-specific perturbations in the mitochondrial function of macrophages infected with Mycobacterium tuberculosis","volume":"3","author":"Jamwal","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1099\/00221287-148-10-3129","article-title":"Dissection of the heat-shock response in Mycobacterium tuberculosis using mutants and microarrays","volume":"148","author":"Stewart","year":"2002","journal-title":"Microbiology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1099\/mic.0.28924-0","article-title":"Regulation of the expression of whiB1 in Mycobacterium tuberculosis: Role of cAMP receptor protein","volume":"152","author":"Agarwal","year":"2006","journal-title":"Microbiology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1365-2958.2008.06541.x","article-title":"Rv1675c (cmr) regulates intramacrophage and cyclic AMP-induced gene expression in Mycobacterium tuberculosis-complex mycobacteria","volume":"71","author":"Gazdik","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1128\/IAI.00614-08","article-title":"Evidence for pore formation in host cell membranes by ESX-1-secreted ESAT-6 and its role in Mycobacterium marinum escape from the vacuole","volume":"76","author":"Smith","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s10495-012-0792-4","article-title":"Mycobacterium kansasii-induced death of murine macrophages involves endoplasmic reticulum stress responses mediated by reactive oxygen species generation or calpain activation","volume":"18","author":"Lim","year":"2013","journal-title":"Apoptosis"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1128\/IAI.02153-14","article-title":"Homeostasis of N-\u03b1-terminal acetylation of EsxA correlates with virulence in Mycobacterium marinum","volume":"82","author":"Champion","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Augenstreich, J., Simeone, R., Wegener, A., Sayes, F., Le, F., Christian, C., Malaga, W., Guilhot, C., Brosch, R., and Astarie, C. (2017). ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis. Cell. Microbiol., 1\u201319.","DOI":"10.1111\/cmi.12726"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e1474","DOI":"10.1038\/cddis.2014.394","article-title":"Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx, necrosis and neutrophil extracellular trap formation","volume":"5","author":"Francis","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Jamwal, S.V., Mehrotra, P., Singh, A., Siddiqui, Z., and Basu, A. (2016). Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism. Sci. Rep., 1\u20139.","DOI":"10.1038\/srep23089"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Clemmensen, H.S., Peter, N., Knudsen, H., Rasmussen, E.M., Winkler, J., Rosenkrands, I., Ahmad, A., Lillebaek, T., Sherman, D.R., and Andersen, P.L. (2017). An attenuated Mycobacterium tuberculosis clinical strain with a defect in ESX-1 secretion induces minimal host immune responses and pathology. Sci. Rep., 1\u201313.","DOI":"10.1038\/srep46666"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s00284-013-0507-2","article-title":"Comparative genomic and proteomic anatomy of Mycobacterium ubiquitous Esx family proteins: Implications in pathogenicity and virulence","volume":"68","author":"Deng","year":"2014","journal-title":"Curr. Microbiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/j.1365-2958.2009.06821.x","article-title":"ESX-1 secreted virulence factors are recognized by multiple cytosolic AAA ATPases in mycobactria","volume":"73","author":"Champion","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/JB.06417-11","article-title":"EspD is critical for the virulence-mediating ESX-1 secretion system in Mycobacterium tuberculosis","volume":"194","author":"Chen","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1126\/science.1132537","article-title":"Microbiology. Mycobacteria\u2019s export strategy","volume":"313","author":"Ize","year":"2006","journal-title":"Science"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"10676","DOI":"10.1073\/pnas.0504922102","article-title":"Mutually dependent secretion of proteins required for mycobacterial virulence","volume":"102","author":"Fortune","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1371\/journal.ppat.1000957","article-title":"EspA acts as a critical mediator of ESX1-dependent virulence in Mycobacterium tuberculosis by affecting bacterial cell wall integrity","volume":"6","author":"Garces","year":"2010","journal-title":"PLoS Pathog."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/mmi.13579","article-title":"Micro commentary discovery of the type VII ESX-1 secretion needle?","volume":"103","author":"Ates","year":"2017","journal-title":"Mol. Microbiol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/mmi.13575","article-title":"EspC forms a filamentous structure in the cell envelope of Mycobacterium tuberculosis and impacts ESX-1 secretion","volume":"103","author":"Lou","year":"2017","journal-title":"Mol. Microbiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.chom.2010.02.006","article-title":"Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence","volume":"7","author":"Ohol","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_155","first-page":"1","article-title":"Mycosins are required for the stabilization of the ESX-1 and ESX-5","volume":"7","author":"Ummels","year":"2016","journal-title":"mBio"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1128\/JB.01074-07","article-title":"PhoP-PhoP interaction at adjacent PhoP binding sites is influenced by protein phosphorylation","volume":"190","author":"Sinha","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1046\/j.1365-2958.2001.02500.x","article-title":"An essential role for phoP in Mycobacterium tuberculosis virulence","volume":"41","author":"Samper","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/mmi.13635","article-title":"Mycobacterium tuberculosis virulence-regulator PhoP interacts with alternative sigma factor SigE during acid-stress response","volume":"104","author":"Bansal","year":"2017","journal-title":"Mol. Microbiol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1128\/JB.00038-13","article-title":"Polyphosphate deficiency in Mycobacterium tuberculosis is associated with enhanced drug susceptibility and impaired growth in guinea pigs","volume":"195","author":"Singh","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1365-2958.2007.05814.x","article-title":"Polyphosphate kinase is involved in stress-induced mprAB-sigE-rel signalling in mycobacteria","volume":"65","author":"Sureka","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1128\/MMBR.05004-11","article-title":"Adaptation to environmental stimuli within the host: Two-component signal transduction systems of Mycobacterium tuberculosis","volume":"75","author":"Bretl","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"19018","DOI":"10.1074\/jbc.M116.746289","article-title":"EspR-dependent ESAT-6 protein secretion of Mycobacterium tuberculosis requires the presence of virulence regulator PhoP","volume":"291","author":"Kumar","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nrmicro.2016.131","article-title":"ESX secretion systems: Mycobacterial evolution to counter host immunity","volume":"14","author":"Sayes","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Bitter, W., Houben, E.N.G., Bottai, D., Brodin, P., Brown, E.J., Cox, J.S., Derbyshire, K., Fortune, S.M., Gao, L.-Y., and Liu, J. (2009). Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000507"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"8320","DOI":"10.1093\/nar\/gku548","article-title":"Genomic mapping of cAMP receptor protein (CRPMt) in Mycobacterium tuberculosis: Relation to transcriptional start sites and the role of CRPMt as a transcription factor","volume":"42","author":"Kahramanoglou","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"6028","DOI":"10.1128\/JB.00469-07","article-title":"ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP-10 under acidic conditions and exhibits membrane-lysing activity","volume":"189","author":"Fretz","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Blasco, B., Chen, J.M., Hartkoorn, R., Sala, C., Uplekar, S., Rougemont, J., Pojer, F., and Cole, S.T. (2012). Virulence regulator EspR of Mycobacterium tuberculosis is a nucleoid-associated protein. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002621"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"24053","DOI":"10.1074\/jbc.M112.364851","article-title":"The dormancy regulator DosR controls ribosome stability in hypoxic mycobacteria","volume":"287","author":"Trauner","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1039\/B912129C","article-title":"A systems perspective of host-pathogen interactions: Predicting disease outcome in tuberculosis","volume":"6","author":"Raman","year":"2010","journal-title":"Mol. Biosyst."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jtbi.2011.03.022","article-title":"A hybrid multi-compartment model of granuloma formation and T cell priming in tuberculosis","volume":"280","author":"Marino","year":"2011","journal-title":"J. Theor. Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1128\/JB.00926-09","article-title":"The Mycobacterium tuberculosis DosR regulon assists in metabolic homeostasis and enables rapid recovery from nonrespiring dormancy","volume":"192","author":"Leistikow","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Gautam, U.S., Chauhan, S., and Tyagi, J.S. (2011). Determinants outside the DevR C-terminal domain are essential for cooperativity and robust activation of dormancy genes in Mycobacterium tuberculosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016500"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1128\/JB.01308-07","article-title":"Cooperative binding of phosphorylated DevR to upstream sites is necessary and sufficient for activation of the Rv3134c-devRS operon in Mycobacterium tuberculosis: Implication in the induction of DevR target genes","volume":"190","author":"Chauhan","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"7400","DOI":"10.1093\/nar\/gkr375","article-title":"Comprehensive insights into Mycobacterium tuberculosis DevR (DosR) regulon activation switch","volume":"39","author":"Chauhan","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0160723","article-title":"Mycobacterium tuberculosis DevR\/DosR dormancy regulator activation mechanism: Dispensability of phosphorylation, cooperativity and essentiality of \u03b110 Helix","volume":"11","author":"Sharma","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"11568","DOI":"10.1073\/pnas.0705054104","article-title":"Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor","volume":"104","author":"Kumar","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1128\/IAI.01449-08","article-title":"Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium tuberculosis dormancy","volume":"77","author":"Honaker","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1111\/febs.13787","article-title":"DevS\/DosS sensor is bifunctional and its phosphatase activity precludes aerobic DevR\/DosR regulon expression in Mycobacterium tuberculosis","volume":"283","author":"Kaur","year":"2016","journal-title":"FEBS J."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"6447","DOI":"10.1128\/JB.00978-10","article-title":"DosS responds to a reduced electron transport system to induce the Mycobacterium tuberculosis DosR regulon","volume":"192","author":"Honaker","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"18032","DOI":"10.1074\/jbc.M802274200","article-title":"Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon","volume":"283","author":"Kumar","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1128\/IAI.00251-13","article-title":"Heme catabolism by heme oxygenase-1 confers host resistance to Mycobacterium infection","volume":"81","author":"Appelberg","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4310","DOI":"10.1073\/pnas.1422387112","article-title":"A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography","volume":"112","author":"Bunker","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nsb845","article-title":"Dimerization allows DNA target site recognition by the NarL response regulator","volume":"9","author":"Maris","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s12275-012-2050-4","article-title":"Protein-protein interactions between histidine kinases and response regulators of Mycobacterium tuberculosis H37Rv","volume":"50","author":"Lee","year":"2012","journal-title":"J. Microbiol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1128\/IAI.00611-13","article-title":"The intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria","volume":"81","author":"Jung","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"10101","DOI":"10.1074\/jbc.M112.448399","article-title":"A new way to degrade heme: The Mycobacterium tuberculosis enzyme MhuD catalyzes heme degradation without generating CO","volume":"288","author":"Nambu","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"29987","DOI":"10.1074\/jbc.M113.507301","article-title":"Truncated hemoglobin, HbN, is post-translationally modified in Mycobacterium tuberculosis and modulates host-pathogen interactions during intracellular infection","volume":"288","author":"Arya","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"5051","DOI":"10.1073\/pnas.1009516108","article-title":"Discovery and characterization of a unique mycobacterial heme acquisition system","volume":"108","author":"Tullius","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1128\/AEM.01984-12","article-title":"Comparative analysis of mycobacterial truncated hemoglobin promoters and the groEL2 promoter in free-living and intracellular mycobacteria","volume":"78","author":"Joseph","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1074\/jbc.M115.662593","article-title":"Lipoprotein LprI of Mycobacterium tuberculosis acts as a lysozyme inhibitor","volume":"291","author":"Sethi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1128\/AAC.43.5.1042","article-title":"Antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis","volume":"43","author":"Phetsuksiri","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/pro.533","article-title":"Structure of Mycobacterium tuberculosis thioredoxin in complex with quinol inhibitor PMX464","volume":"20","author":"Hall","year":"2011","journal-title":"Protein Sci."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Ascenzi, P., Coletta, A., Cao, Y., Trezza, V., Leboffe, L., Fanali, G., Fasano, M., Pesce, A., Ciaccio, C., and Marini, S. (2013). Isoniazid inhibits the heme-based reactivity of Mycobacterium tuberculosis truncated hemoglobin N. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069762"},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Tan, M.P., Sequeira, P., Lin, W.W., Phong, W.Y., Cliff, P., Ng, S.H., Lee, B.H., Camacho, L., Schnappinger, D., and Ehrt, S. (2010). Nitrate respiration protects hypoxic Mycobacterium tuberculosis against acid- and reactive nitrogen species stresses. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013356"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1099\/mic.0.054759-0","article-title":"Nitrate reduction pathways in mycobacteria and their implications during latency","volume":"158","author":"Khan","year":"2012","journal-title":"Microbiology"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Rustad, T.R., Harrell, M.I., Liao, R., and Sherman, D.R. (2008). The enduring hypoxic response of Mycobacterium tuberculosis. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001502"},{"key":"ref_197","unstructured":"Veatch, A.V., and Kaushal, D. (2017). Opening Pandora\u2019s Box: Mechanisms of Mycobacterium tuberculosis Resuscitation. Trends Microbiol., 1\u201313."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00284-014-0736-z","article-title":"CRP acts as a transcriptional repressor of the YPO1635- phoPQ-YPO1632 operon in Yersinia pestis","volume":"70","author":"Zhang","year":"2015","journal-title":"Curr. Microbiol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1099\/mic.0.037622-0","article-title":"Comparative expression analysis of rpf-like genes of Mycobacterium tuberculosis H37Rv under different physiological stress and growth conditions","volume":"156","author":"Gupta","year":"2010","journal-title":"Microbiology"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"7795","DOI":"10.1128\/JB.187.22.7795-7804.2005","article-title":"Characterization of Mycobacterium tuberculosis Rv3676 (CRP Mt), a cyclic AMP receptor protein-like DNA binding protein","volume":"187","author":"Bai","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1111\/j.1365-2958.2005.04609.x","article-title":"A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor","volume":"56","author":"Rickman","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1128\/IAI.00520-12","article-title":"MprA and DosR coregulate a Mycobacterium tuberculosis virulence operon encoding Rv1813c and Rv1812c","volume":"80","author":"Bretl","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"S142","DOI":"10.1016\/j.tube.2011.10.024","article-title":"The \u03b2-propeller gene Rv1057 of Mycobacterium tuberculosis has a complex promoter directly regulated by both the MprAB and TrcRS two-component systems","volume":"91","author":"Pang","year":"2011","journal-title":"Tuberculosis"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1099\/mic.0.29281-0","article-title":"Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis","volume":"153","author":"Pang","year":"2007","journal-title":"Microbiology"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1128\/JB.01530-12","article-title":"Autoregulation of PhoP\/PhoQ and positive regulation of the cyclic AMP receptor protein-cyclic AMP complex by PhoP in Yersinia pestis","volume":"195","author":"Zhang","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_206","first-page":"1","article-title":"RpoS integrates CRP, Fis, and PhoP signaling pathways to control Salmonella Typhi hlyE expression","volume":"14","author":"Villagra","year":"2014","journal-title":"BMC Microbiol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"16085","DOI":"10.1073\/pnas.0406909101","article-title":"Inorganic polyphosphate in the origin and survival of species","volume":"101","author":"Brown","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"6460","DOI":"10.1128\/AAC.01139-16","article-title":"Stringent response factors PPX1 and PPK2 play an important role in Mycobacterium tuberculosis metabolism, biofilm formation, and sensitivity to isoniazid in vivo","volume":"60","author":"Chuang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1099\/mic.0.068452-0","article-title":"Polyphosphate kinase 1, a central node in the stress response network of Mycobacterium tuberculosis, connects the two-component systems MprAB and SenX3-RegX3 and the extracytoplasmic function sigma factor, sigma E","volume":"159","author":"Sanyal","year":"2013","journal-title":"Microbiology"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/j.1365-2958.2009.07009.x","article-title":"An integrated regulatory network including two positive feedback loops to modulate the activity of SigE in mycobacteria","volume":"75","author":"Manganelli","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.tube.2017.07.009","article-title":"Mycobacterium tuberculosis sigE mutant ST28 used as a vaccine induces protective immunity in the guinea pig model","volume":"106","author":"Troudt","year":"2017","journal-title":"Tuberculosis"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"VanderVen, B.C., Fahey, R.J., Lee, W., Liu, Y., Abramovitch, R.B., Memmott, C., Crowe, A.M., Eltis, L.D., Perola, E., and Deininger, D.D. (2015). Novel inhibitors of cholesterol degradation in Mycobacterium tuberculosis reveal how the bacterium\u2019s metabolism is constrained by the intracellular environment. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004679"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1128\/MMBR.00052-12","article-title":"Role of pore-forming toxins in bacterial infectious diseases","volume":"77","author":"Los","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1126\/science.288.5471.1647","article-title":"Essential role for cholesterol in entry of mycobacteria into macrophages","volume":"288","author":"Gatfield","year":"2000","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/2\/347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:52:25Z","timestamp":1760194345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/2\/347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,24]]},"references-count":214,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["ijms19020347"],"URL":"https:\/\/doi.org\/10.3390\/ijms19020347","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,24]]}}}