{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T02:00:00Z","timestamp":1784426400829,"version":"3.55.0"},"reference-count":93,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Potts Memorial Foundation Grant","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]},{"name":"Professional Staff Congress-City University of New York Award","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]},{"name":"Weill Cornell Medical College Howard and Abby Milstein Program in Chemical Biology","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]},{"name":"City University of New York Doctoral Student Research Grant Program Awards","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]},{"name":"Alfred Alberts Award in Biochemistry and a Lila Lustig Science Scholarship","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]},{"name":"Estelle and James Ramey Scholarships","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]},{"name":"Sandi Sulam Memorial Award","award":["65408-00 53"],"award-info":[{"award-number":["65408-00 53"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The opportunistic pathogen Mycobacterium abscessus subsp. abscessus (Mab) has become an emerging public health threat due to the increasing number of Mab-associated chronic pulmonary disease cases. Treatment requires multiple drug courses and is often combined with surgical resection. Cure rates are only ~50% due to treatment failure and comorbidities. Deeper understanding of the biology of Mab is required to illuminate potential avenues for the development of better therapeutics against Mab infections. The ESX-3 type VII protein secretion system of Mab has an important role in host inflammatory and pathological responses during infection. In this work, we demonstrate a functional link between ESX-3 and an iron uptake system based on an unusual mycobactin-type siderophore (designated MBT Ab) and exploit this link to implement a large screen for transposon mutants with an impaired ESX-3. Most mutants we identified carry insertions in genes encoding predicted ESX-3 secretion machinery components or potential ESX-3 substrates. The mutants overproduce MBT Ab, a trait consistent with an iron uptake defect. Our characterization of MBT Ab revealed structural features reminiscent of nocardial mycobactin-like compounds with cytotoxicity. This finding raises the possibility that MBT Ab may play roles in pathogenesis unlinked to iron homeostasis. The mutants generated herein will facilitate research to better understand the role of ESX-3 and its interplay with the siderophore system.<\/jats:p>","DOI":"10.3390\/pathogens11090953","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:22:48Z","timestamp":1661300568000},"page":"953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mycobacterium abscessus Mutants with a Compromised Functional Link between the Type VII ESX-3 System and an Iron Uptake Mechanism Reliant on an Unusual Mycobactin Siderophore"],"prefix":"10.3390","volume":"11","author":[{"given":"Glennon V.","family":"Bythrow","sequence":"first","affiliation":[{"name":"Department of Biology, Brooklyn College, City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"},{"name":"Biology Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9995-6736","authenticated-orcid":false,"given":"Manal F.","family":"Farhat","sequence":"additional","affiliation":[{"name":"Department of Biology, Brooklyn College, City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"},{"name":"Biology Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Levendosky","sequence":"additional","affiliation":[{"name":"Department of Biology, Brooklyn College, City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"},{"name":"Biology Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poornima","family":"Mohandas","sequence":"additional","affiliation":[{"name":"Department of Biology, Brooklyn College, City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"},{"name":"Biology Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle A.","family":"Germain","sequence":"additional","affiliation":[{"name":"Department of Biology, Brooklyn College, City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"},{"name":"Biology Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barney","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E. N.","family":"Quadri","sequence":"additional","affiliation":[{"name":"Department of Biology, Brooklyn College, City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, USA"},{"name":"Biology Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"},{"name":"Biochemistry Program, Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.tim.2009.12.007","article-title":"Mycobacterium abscessus: A new player in the mycobacterial field","volume":"18","author":"Medjahed","year":"2010","journal-title":"Trends Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0732-8893(00)00211-X","article-title":"Disseminated Mycobacterium abscessus infection manifesting as fever of unknown origin and intra-abdominal lymphadenitis: Case report and literature review","volume":"39","author":"Mueller","year":"2001","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"312","DOI":"10.5144\/0256-4947.2012.312","article-title":"First case report of chronic pulmonary lung disease caused by Mycobacterium abscessus in two immunocompetent patients in Saudi Arabia","volume":"32","author":"Varghese","year":"2012","journal-title":"Ann. Saudi Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1600-0463.2006.apm_390.x","article-title":"Mycobacterium abscessus: An emerging rapid-growing potential pathogen","volume":"114","author":"Petrini","year":"2006","journal-title":"APMIS"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1164\/rccm.201003-0395OC","article-title":"Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus","volume":"183","author":"Koh","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1093\/jac\/dkr578","article-title":"Mycobacterium abscessus: A new antibiotic nightmare","volume":"67","author":"Nessar","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4471","DOI":"10.1099\/ijsem.0.001376","article-title":"Emended description of Mycobacterium abscessus, Mycobacterium abscessus subsp. abscessus and Mycobacterium abscessus subsp. bolletii and designation of Mycobacterium abscessus subsp. massiliense comb. nov","volume":"66","author":"Tortoli","year":"2016","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3389\/fimmu.2020.00303","article-title":"The rise of non-tuberculosis mycobacterial lung disease","volume":"11","author":"Ratnatunga","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0272-5231(02)00021-7","article-title":"Pulmonary disease caused by rapidly growing mycobacteria","volume":"23","author":"Daley","year":"2002","journal-title":"Clin. Chest Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1148\/radiol.2313030833","article-title":"Nontuberculous mycobacterial pulmonary infection in immunocompetent patients: Comparison of thin-section CT and histopathologic findings","volume":"231","author":"Jeong","year":"2004","journal-title":"Radiology"},{"key":"ref_11","first-page":"499","article-title":"Nontuberculous mycobacterial lung disease in southern Taiwan","volume":"32","author":"Wang","year":"2009","journal-title":"Chang Gung Med. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1086\/655140","article-title":"Rapidly growing mycobacteria infection in patients with cancer","volume":"51","author":"Sepkowitz","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1164\/rccm.200604-571ST","article-title":"An official ATS\/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases","volume":"175","author":"Griffith","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.drup.2012.04.001","article-title":"Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria","volume":"15","author":"Boeree","year":"2012","journal-title":"Drug Resist. Updates"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4346","DOI":"10.2174\/1381612819666131118170717","article-title":"Targeting type VII\/ESX secretion systems for development of novel antimycobacterial drugs","volume":"20","author":"Bottai","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.2217\/fmb.10.112","article-title":"Protein export systems of Mycobacterium tuberculosis: Novel targets for drug development?","volume":"5","author":"Feltcher","year":"2010","journal-title":"Future Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Newton-Foot, M., Warren, R.M., Sampson, S.L., van Helden, P.D., and Gey van Pittius, N.C. (2016). The plasmid-mediated evolution of the mycobacterial ESX (Type VII) secretion systems. BMC Evol. Biol., 16.","DOI":"10.1186\/s12862-016-0631-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41579-021-00560-5","article-title":"Type VII secretion systems: Structure, functions and transport models","volume":"19","author":"Famelis","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1128\/microbiolspec.VMBF-0011-2015","article-title":"Type VII secretion: A highly versatile secretion system","volume":"4","author":"Ates","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_20","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":"Groschel","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bitter, W., Houben, E.N., 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_22","doi-asserted-by":"crossref","unstructured":"Serafini, A., Pisu, D., Palu, G., Rodriguez, G.M., and Manganelli, R. (2013). The ESX-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078351"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1046\/j.1365-2958.2003.03425.x","article-title":"Genes required for mycobacterial growth defined by high density mutagenesis","volume":"48","author":"Sassetti","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_24","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_25","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_26","doi-asserted-by":"crossref","first-page":"e01073-14","DOI":"10.1128\/mBio.01073-14","article-title":"Mycobacterial Esx-3 requires multiple components for iron acquisition","volume":"5","author":"Siegrist","year":"2014","journal-title":"mBio"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"29993","DOI":"10.1074\/jbc.M111.248732","article-title":"Solution structure of the Mycobacterium tuberculosis EsxG.EsxH 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_29","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nm.2420","article-title":"A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against Mycobacterium tuberculosis","volume":"17","author":"Sweeney","year":"2011","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.4049\/jimmunol.179.6.3973","article-title":"Induction of CD8 T cells against a novel epitope in TB10.4: Correlation with mycobacterial virulence and the presence of a functional region of difference-1","volume":"179","author":"Billeskov","year":"2007","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1128\/IAI.02086-05","article-title":"High frequency of CD4+ T cells specific for the TB10.4 protein correlates with protection against Mycobacterium tuberculosis infection","volume":"74","author":"Majlessi","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1128\/IAI.70.10.5446-5453.2002","article-title":"Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family","volume":"70","author":"Skjot","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","unstructured":"Zhang, L., Hendrickson, R.C., Meikle, V., Lefkowitz, E.J., Ioerger, T.R., and Niederweis, M. (2020). Comprehensive analysis of iron utilization by Mycobacterium tuberculosis. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008337"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"230","DOI":"10.2174\/187152607782110040","article-title":"Strategic paradigm shifts in the antimicrobial drug discovery process of the 21st century","volume":"7","author":"Quadri","year":"2007","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.micinf.2016.09.001","article-title":"Mycobacterium abscessus ESX-3 plays an important role in host inflammatory and pathological responses during infection","volume":"19","author":"Kim","year":"2017","journal-title":"Microbes Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e0104921","DOI":"10.1128\/mBio.01049-21","article-title":"Genome-wide essentiality analysis of Mycobacterium abscessus by saturated transposon mutagenesis and deep sequencing","volume":"12","author":"Rifat","year":"2021","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1128\/jcm.30.5.1225-1231.1992","article-title":"Mycobactin analysis as an aid for the identification of Mycobacterium fortuitum and Mycobacterium chelonae subspecies","volume":"30","author":"Bosne","year":"1992","journal-title":"J. Clin. Microbiol."},{"key":"ref_39","first-page":"1883","article-title":"Mycobactins as chemotaxonomic characters for some rapidly growing mycobacteria","volume":"130","author":"Hall","year":"1984","journal-title":"J. Gen. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ripoll, F., Pasek, S., Schenowitz, C., Dossat, C., Barbe, V., Rottman, M., Macheras, E., Heym, B., Herrmann, J.L., and Daffe, M. (2009). Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005660"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3109\/10409238.2014.896859","article-title":"Biosynthesis of mycobacterial lipids by polyketide synthases and beyond","volume":"49","author":"Quadri","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S1074-5521(98)90291-5","article-title":"Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin","volume":"5","author":"Quadri","year":"1998","journal-title":"Chem. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.1128\/JB.05811-11","article-title":"Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster","volume":"193","author":"Chavadi","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1021\/acs.biochem.8b01153","article-title":"Kinetic analyses of the siderophore biosynthesis inhibitor salicyl-AMS and analogues as MbtA inhibitors and antimycobacterial agents","volume":"58","author":"Bythrow","year":"2019","journal-title":"Biochemistry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nchembio706","article-title":"Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis","volume":"1","author":"Ferreras","year":"2005","journal-title":"Nat. Chem. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.1021\/acs.orglett.8b02832","article-title":"Total synthesis of the proposed structure of mycobactin J","volume":"20","author":"Ghosh","year":"2018","journal-title":"Org. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e02133-16","DOI":"10.1128\/mBio.02133-16","article-title":"Comprehensive essentiality analysis of the Mycobacterium tuberculosis genome via saturating transposon mutagenesis","volume":"8","author":"DeJesus","year":"2017","journal-title":"mBio"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-019-1633-1","article-title":"Architecture of the mycobacterial type VII secretion system","volume":"576","author":"Famelis","year":"2019","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e52983","DOI":"10.7554\/eLife.52983","article-title":"The structure of the endogenous ESX-3 secretion system","volume":"8","author":"Poweleit","year":"2019","journal-title":"eLife"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14339","DOI":"10.1073\/pnas.2036282100","article-title":"Comprehensive transposon mutant library of Pseudomonas aeruginosa","volume":"100","author":"Jacobs","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8736","DOI":"10.1073\/pnas.0803281105","article-title":"A defined transposon mutant library and its use in identifying motility genes in Vibrio cholerae","volume":"105","author":"Cameron","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e00604","DOI":"10.1128\/mBio.00604-13","article-title":"Sequence-defined transposon mutant library of Burkholderia thailandensis","volume":"4","author":"Gallagher","year":"2013","journal-title":"mBio"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1073\/pnas.0606713104","article-title":"A comprehensive transposon mutant library of Francisella novicida, a bioweapon surrogate","volume":"104","author":"Gallagher","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e988","DOI":"10.1002\/mbo3.988","article-title":"Transposon mutagenesis in Mycobacterium kansasii links a small RNA gene to colony morphology and biofilm formation and identifies 9,885 intragenic insertions that do not compromise colony outgrowth","volume":"9","author":"Budell","year":"2020","journal-title":"Microbiologyopen"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"fnw016","DOI":"10.1093\/femsle\/fnw016","article-title":"Pleiotropic consequences of gene knockouts in the phthiocerol dimycocerosate and phenolic glycolipid biosynthetic gene cluster of the opportunistic human pathogen Mycobacterium marinum","volume":"363","author":"Mohandas","year":"2016","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Maciag, A., Piazza, A., Riccardi, G., and Milano, A. (2009). Transcriptional analysis of ESAT-6 cluster 3 in Mycobacterium smegmatis. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-48"},{"key":"ref_57","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_58","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_59","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1016\/j.febslet.2006.03.090","article-title":"Comparative analysis of iron regulated genes in mycobacteria","volume":"580","author":"Yellaboina","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1099\/mic.0.031948-0","article-title":"Identification and functional characterization of the iron-dependent regulator (IdeR) of Mycobacterium avium subsp. paratuberculosis","volume":"155","author":"Janagama","year":"2009","journal-title":"Microbiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1093\/bioinformatics\/bti375","article-title":"Computational prediction and experimental verification of novel IdeR binding sites in the upstream sequences of Mycobacterium tuberculosis open reading frames","volume":"21","author":"Prakash","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e13163","DOI":"10.1111\/cmi.13163","article-title":"Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes","volume":"22","author":"Knobloch","year":"2020","journal-title":"Cell. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1128\/JB.181.15.4443-4451.1999","article-title":"Iron acquisition and metabolism by mycobacteria","volume":"181","author":"Rutter","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1073\/pnas.0507924103","article-title":"A genetic locus required for iron acquisition in Mycobacterium tuberculosis","volume":"103","author":"Krithika","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Madigan, C.A., Martinot, A.J., Wei, J.R., Madduri, A., Cheng, T.Y., Young, D.C., Layre, E., Murry, J.P., Rubin, E.J., and Moody, D.B. (2015). Lipidomic analysis links mycobactin synthase K to iron uptake and virulence in M. tuberculosis. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004792"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000343343","article-title":"Comparative genomic insights into the biosynthesis and regulation of mycobacterial siderophores","volume":"31","author":"Li","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-4939-2450-9_18","article-title":"A multi-stress model for high throughput screening against non-replicating Mycobacterium tuberculosis","volume":"1285","author":"Gold","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Joshi, H., Dave, R., and Venugopalan, V.P. (2014). Protein as chemical cue: Non-nutritional growth enhancement by exogenous protein in Pseudomonas putida KT2440. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103730"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1021\/bi00305a003","article-title":"Effect of serum albumin on siderophore-mediated utilization of transferrin iron","volume":"23","author":"Konopka","year":"1984","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"14758","DOI":"10.1073\/pnas.1409345111","article-title":"Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion","volume":"111","author":"Ekiert","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jmb.2018.11.003","article-title":"Structural variability of EspG chaperones from mycobacterial ESX-1, ESX-3, and ESX-5 type VII secretion systems","volume":"431","author":"Tuukkanen","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/gbe\/evw001","article-title":"Mycobacterial pan-genome analysis suggests important role of plasmids in the radiation of type VII secretion systems","volume":"8","author":"Dumas","year":"2016","journal-title":"Genome Biol. Evol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17681","DOI":"10.1074\/jbc.M800123200","article-title":"Molecular features governing the stability and specificity of functional complex formation by Mycobacterium tuberculosis CFP-10\/ESAT-6 family proteins","volume":"283","author":"Lightbody","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1038\/sj.emboj.7600732","article-title":"Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6","volume":"24","author":"Renshaw","year":"2005","journal-title":"EMBO J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.bbapap.2017.04.001","article-title":"Characterization of EccA3, a CbbX family ATPase from the ESX-3 secretion pathway of M. tuberculosis","volume":"1865","author":"Gaur","year":"2017","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/bioinformatics\/btt043","article-title":"Bayesian analysis of gene essentiality based on sequencing of transposon insertion libraries","volume":"29","author":"DeJesus","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"9033","DOI":"10.1093\/nar\/gkt654","article-title":"High-resolution definition of the Vibrio cholerae essential gene set with Hidden Markov Model-based analyses of transposon-insertion sequencing data","volume":"41","author":"Chao","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_78","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_79","doi-asserted-by":"crossref","first-page":"24616","DOI":"10.1074\/jbc.M111.247601","article-title":"Inactivation of tesA reduces cell-wall lipid production and increases drug susceptibility in mycobacteria","volume":"286","author":"Chavadi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_80","unstructured":"Sambrook, J., and Russell, D.W. (2001). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Pres. [3rd ed.]."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Medjahed, H., and Singh, A.K. (2010). Genetic manipulation of Mycobacterium abscessus. Current Protocols in Microbiology, John Wiley & Sons, Inc.","DOI":"10.1002\/9780471729259.mc10d02s18"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.gene.2010.09.005","article-title":"An improved counterselectable marker system for mycobacterial recombination using galK and 2-deoxy-galactose","volume":"470","author":"Barkan","year":"2011","journal-title":"Gene"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1432-1033.1991.tb16326.x","article-title":"Analysis of the complex transcription termination region of the Escherichia coli rrnB gene","volume":"201","author":"Orosz","year":"1991","journal-title":"Eur. J. Biochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/978-1-4939-2450-9_7","article-title":"Electroporation of mycobacteria","volume":"1285","author":"Goude","year":"2015","journal-title":"Methods. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1128\/JB.00216-07","article-title":"Silencing Mycobacterium smegmatis by using tetracycline repressors","volume":"189","author":"Guo","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1007\/s00253-011-3633-4","article-title":"Optimized compatible set of BioBrick vectors for metabolic pathway engineering","volume":"92","author":"Vick","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.gene.2010.07.012","article-title":"Taking phage integration to the next level as a genetic tool for mycobacteria","volume":"468","author":"Huff","year":"2010","journal-title":"Gene"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"27292","DOI":"10.1074\/jbc.270.45.27292","article-title":"The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2","volume":"270","author":"George","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1093\/bioinformatics\/bti635","article-title":"Virtual Footprint and PRODORIC: An integrative framework for regulon prediction in prokaryotes","volume":"21","author":"Munch","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"D366","DOI":"10.1093\/nar\/gks1241","article-title":"OrtholugeDB: A bacterial and archaeal orthology resource for improved comparative genomic analysis","volume":"41","author":"Whiteside","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.1016\/j.bmcl.2011.08.052","article-title":"Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide-polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis","volume":"21","author":"Ferreras","year":"2011","journal-title":"Bioorgan. Med. Chem. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.1128\/AAC.00918-13","article-title":"Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice","volume":"57","author":"Lun","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1073\/pnas.92.11.5189","article-title":"Iron acquisition by Mycobacterium tuberculosis: Isolation and characterization of a family of iron-binding exochelins","volume":"92","author":"Gobin","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/9\/953\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:13:53Z","timestamp":1760141633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/9\/953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,23]]},"references-count":93,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["pathogens11090953"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11090953","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,23]]}}}