{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:45:43Z","timestamp":1792215943119,"version":"4.4.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Mycobacterium abscessus<\/jats:italic> (<jats:italic>Mab<\/jats:italic>) is an opportunistic pathogen afflicting individuals with underlying lung disease such as Cystic Fibrosis (CF) or immunodeficiencies. Current treatment strategies for <jats:italic>Mab<\/jats:italic> infections are limited by its inherent antibiotic resistance and limited drug access to <jats:italic>Mab<\/jats:italic> in its <jats:italic>in vivo<\/jats:italic> niches resulting in poor cure rates of 30-50%. <jats:italic>Mab\u2019s<\/jats:italic> ability to survive within macrophages, granulomas and the mucus laden airways of the CF lung requires adaptation via transcriptional remodeling to counteract stresses like hypoxia, increased levels of nitrate, nitrite, and reactive nitrogen intermediates. <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>Mtb<\/jats:italic>) is known to coordinate hypoxic adaptation via induction of respiratory nitrate assimilation through the nitrate reductase <jats:italic>narGHJI<\/jats:italic>. <jats:italic>Mab<\/jats:italic>, on the other hand, does not encode a respiratory nitrate reductase. In addition, our recent study of the transcriptional responses of <jats:italic>Mab<\/jats:italic> to hypoxia revealed marked down-regulation of a locus containing putative nitrate assimilation genes, including the orphan response regulator <jats:italic>nnaR<\/jats:italic> (nitrate\/nitrite assimilation regulator). These putative nitrate assimilation genes, <jats:italic>narK3<\/jats:italic> (nitrate\/nitrite transporter), <jats:italic>nirBD<\/jats:italic> (nitrite reductase), <jats:italic>nnaR<\/jats:italic>, and <jats:italic>sirB<\/jats:italic> (ferrochelatase) are arranged contiguously while <jats:italic>nasN<\/jats:italic> (assimilatory nitrate reductase identified in this work) is encoded in a different locus. Absence of a respiratory nitrate reductase in <jats:italic>Mab<\/jats:italic> and down-regulation of nitrogen metabolism genes in hypoxia suggest interplay between hypoxia adaptation and nitrate assimilation are distinct from what was previously documented in <jats:italic>Mtb<\/jats:italic>. The mechanisms used by <jats:italic>Mab<\/jats:italic> to fine-tune the transcriptional regulation of nitrogen metabolism in the context of stresses e.g. hypoxia, particularly the role of NnaR, remain poorly understood. To evaluate the role of NnaR in nitrate metabolism we constructed a <jats:italic>Mab nnaR<\/jats:italic> knockout strain (<jats:italic>Mab<jats:sub>\u0394nnaR<\/jats:sub><\/jats:italic>) and complement (<jats:italic>Mab<jats:sub>\u0394nnaR+C<\/jats:sub><\/jats:italic>) to investigate transcriptional regulation and phenotypes. qRT-PCR revealed NnaR is necessary for regulating nitrate and nitrite reductases along with a putative nitrate transporter. Loss of NnaR compromised the ability of <jats:italic>Mab<\/jats:italic> to assimilate nitrate or nitrite as sole nitrogen sources highlighting its necessity. This work provides the first insights into the role of <jats:italic>Mab<\/jats:italic> NnaR setting a foundation for future work investigating NnaR\u2019s contribution to pathogenesis.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1411333","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T04:41:40Z","timestamp":1716525700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Orphan response regulator NnaR is critical for nitrate and nitrite assimilation in Mycobacterium abscessus"],"prefix":"10.3389","volume":"14","author":[{"given":"Breven S.","family":"Simcox","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle H.","family":"Rohde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4592","DOI":"10.1128\/JB.00698-13","article-title":"Nitrite reductase NirBD is induced and plays an important role during in vitro dormancy of Mycobacterium tuberculosis","volume":"195","author":"Akhtar","year":"2013","journal-title":"J. Bacteriol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2016.00038","article-title":"Post-translational serine\/threonine phosphorylation and lysine acetylation: A novel regulatory aspect of the global nitrogen response regulator glnR in S. coelicolor M145","volume":"3","author":"Amin","year":"2016","journal-title":"Front. Mol. Biosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1099\/mic.0.054817-0","article-title":"A novel GlnR target gene, nnaR, is involved in nitrate\/nitrite assimilation in Streptomyces coelicolor","volume":"158","author":"Amin","year":"2012","journal-title":"Microbiol. (Reading)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"17552","DOI":"10.1038\/s41598-018-35844-z","article-title":"The NnaR orphan response regulator is essential for the utilization of nitrate and nitrite as sole nitrogen sources in mycobacteria","volume":"8","author":"Antczak","year":"2018","journal-title":"Sci. Rep."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj3860","article-title":"Therapeutic efficacy of antimalarial drugs targeting DosRS signaling in Mycobacterium abscessus","volume":"14","author":"Belardinelli","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005986","article-title":"Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking","volume":"12","author":"Bernut","year":"2016","journal-title":"PloS Pathog."},{"key":"B7","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1128\/CMR.15.4.716-746.2002","article-title":"Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria","volume":"15","author":"Brown-Elliott","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8699","article-title":"Stepwise pathogenic evolution of Mycobacterium abscessus","volume":"372","author":"Bryant","year":"2021","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4700","DOI":"10.1128\/IAI.67.9.4700-4707.1999","article-title":"Preliminary characterization of a Mycobacterium abscessus mutant in human and murine models of infection","volume":"67","author":"Byrd","year":"1999","journal-title":"Infect. Immun."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0245745","article-title":"Mycobacterium smegmatis does not display functional redundancy in nitrate reductase enzymes","volume":"16","author":"Cardoso","year":"2021","journal-title":"PloS One"},{"key":"B11","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1465-9921-4-8","article-title":"State of the art: why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection","volume":"4","author":"Chmiel","year":"2003","journal-title":"Respir. Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"E4256","DOI":"10.1073\/pnas.1316894110","article-title":"Nitrite produced by Mycobacterium tuberculosis in human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression","volume":"110","author":"Cunningham-Bussel","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00048-16","article-title":"Prokaryotic heme biosynthesis: multiple pathways to a common essential product","volume":"81","author":"Dailey","year":"2017","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jcf.2009.12.001","article-title":"Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis","volume":"9","author":"Esther","year":"2010","journal-title":"J. Cyst Fibros"},{"key":"B15","doi-asserted-by":"publisher","first-page":"107025","DOI":"10.1016\/j.ijantimicag.2023.107025","article-title":"GlnR activated transcription of nitrogen metabolic pathway genes facilitates biofilm formation by mycobacterium abscessus","volume":"63","author":"Fan","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1146\/annurev-micro-020518-115931","article-title":"Structural basis of response regulator function","volume":"73","author":"Gao","year":"2019","journal-title":"Annu. Rev. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s42003-019-0594-0","article-title":"Mycobacterium tuberculosis sensor kinase DosS modulates the autophagosome in a DosR-independent manner","volume":"2","author":"Gautam","year":"2019","journal-title":"Commun. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1128\/JB.00179-11","article-title":"Comparative genomics of the dormancy regulons in mycobacteria","volume":"193","author":"Gerasimova","year":"2011","journal-title":"J. Bacteriol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045459","article-title":"Mutational analysis of the respiratory nitrate transporter NarK2 of Mycobacterium tuberculosis","volume":"7","author":"Giffin","year":"2012","journal-title":"PloS One"},{"key":"B20","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/nrmicro3349","article-title":"Nitrogen metabolism in Mycobacterium tuberculosis physiology and virulence","volume":"12","author":"Gouzy","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/S0169-409X(02)00152-7","article-title":"Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets","volume":"54","author":"Hassett","year":"2002","journal-title":"Adv. Drug Delivery Rev."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00479-22","article-title":"Transcriptional self-regulation of the master nitrogen regulator glnR in mycobacteria","volume":"205","author":"He","year":"2023","journal-title":"J. Bacteriol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"20667","DOI":"10.1074\/jbc.M609104200","article-title":"Structure of an atypical orphan response regulator protein supports a new phosphorylation-independent regulatory mechanism","volume":"282","author":"Hong","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s00284-015-0838-2","article-title":"Phylogenomics of mycobacterium nitrate reductase operon","volume":"71","author":"Huang","year":"2015","journal-title":"Curr. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.1038\/s41467-019-11999-9","article-title":"Translational coupling via termination-reinitiation in archaea and bacteria","volume":"10","author":"Huber","year":"2019","journal-title":"Nat. Commun."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01347-17","article-title":"Mycobacterium abscessus whiB7 regulates a species-specific repertoire of genes to confer extreme antibiotic resistance","volume":"61","author":"Hurst-Hess","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"B27","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1186\/1471-2164-14-301","article-title":"Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis","volume":"14","author":"Jenkins","year":"2013","journal-title":"BMC Genomics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0005-2728(99)00020-1","article-title":"Nitric oxide metabolism and breakdown","volume":"1411","author":"Kelm","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"B29","doi-asserted-by":"publisher","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":"Microbiol. (Reading)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.3201\/2109.141634","article-title":"Mycobacterium abscessus complex infections in humans","volume":"21","author":"Lee","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/1472-6750-11-92","article-title":"FastCloning: a highly simplified, purification-free, sequence- and ligation-independent PCR cloning method","volume":"11","author":"Li","year":"2011","journal-title":"BMC Biotechnol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"15413","DOI":"10.1074\/jbc.M113.543504","article-title":"Atypical OmpR\/PhoB subfamily response regulator GlnR of actinomycetes functions as a homodimer, stabilized by the unphosphorylated conserved Asp-focused charge interactions","volume":"289","author":"Lin","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7030090","article-title":"Mycobacterium abscessus: environmental bacterium turned clinical nightmare","volume":"7","author":"Lopeman","year":"2019","journal-title":"Microorganisms"},{"key":"B34","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/nrmicro929","article-title":"Nitrate, bacteria and human health","volume":"2","author":"Lundberg","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1128\/CMR.15.2.194-222.2002","article-title":"Lung infections associated with cystic fibrosis","volume":"15","author":"Lyczak","year":"2002","journal-title":"Clin. Microbiol. Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1099\/mic.0.023275-0","article-title":"The roles of the nitrate reductase NarGHJI, the nitrite reductase NirBD and the response regulator GlnR in nitrate assimilation of Mycobacterium tuberculosis","volume":"155","author":"Malm","year":"2009","journal-title":"Microbiol. (Reading)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.03120","article-title":"The balance metabolism safety net: integration of stress signals by interacting transcriptional factors in streptomyces and related actinobacteria","volume":"10","author":"Martin","year":"2019","journal-title":"Front. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1186\/s12864-016-2868-y","article-title":"Functional characterization of the Mycobacterium abscessus genome coupled with condition specific transcriptomics reveals conserved molecular strategies for host adaptation and persistence","volume":"17","author":"Miranda-CasoLuengo","year":"2016","journal-title":"BMC Genomics"},{"key":"B39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.mimet.2018.03.020","article-title":"Evaluation of the intracellular activity of drugs against Mycobacterium abscessus using a THP-1 macrophage model","volume":"148","author":"Molina-Torres","year":"2018","journal-title":"J. Microbiol. Methods"},{"key":"B40","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1164\/rccm.200207-678OC","article-title":"Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis","volume":"167","author":"Olivier","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1128\/AEM.03695-12","article-title":"Development of a new generation of vectors for gene expression, gene replacement, and protein-protein interaction studies in mycobacteria","volume":"79","author":"Parikh","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00084","article-title":"Mycobacterial dormancy systems and host responses in tuberculosis","volume":"8","author":"Peddireddy","year":"2017","journal-title":"Front. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/s41467-020-14722-1","article-title":"Siroheme synthase orients substrates for dehydrogenase and chelatase activities in a common active site","volume":"11","author":"Pennington","year":"2020","journal-title":"Nat. Commun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ymben.2017.03.006","article-title":"An integrated network analysis reveals that nitric oxide reductase prevents metabolic cycling of nitric oxide by Pseudomonas aeruginosa","volume":"41","author":"Robinson","year":"2017","journal-title":"Metab. Eng."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1093\/nar\/gkp162","article-title":"Phosphate control over nitrogen metabolism in Streptomyces coelicolor: direct and indirect negative control of glnR, glnA, glnII and amtB expression by the response regulator PhoP","volume":"37","author":"Rodriguez-Garcia","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"B46","doi-asserted-by":"publisher","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":"B47","doi-asserted-by":"publisher","first-page":"8648","DOI":"10.1021\/bi800635y","article-title":"Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex","volume":"47","author":"Schubert","year":"2008","journal-title":"Biochemistry"},{"key":"B48","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.chom.2008.03.007","article-title":"Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection","volume":"3","author":"Shiloh","year":"2008","journal-title":"Cell Host Microbe"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1144210","article-title":"Mycobacterium abscessus DosRS two-component system controls a species-specific regulon required for adaptation to hypoxia","volume":"13","author":"Simcox","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"11346","DOI":"10.1073\/pnas.0602817103","article-title":"Dissecting virulence pathways of Mycobacterium tuberculosis through protein-protein association","volume":"103","author":"Singh","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B51","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3390\/bios3030259","article-title":"The dosS-dosT\/dosR mycobacterial sensor system","volume":"3","author":"Sivaramakrishnan","year":"2013","journal-title":"Biosensors (Basel)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1128\/JB.01857-07","article-title":"Nitrate enhances the survival of Mycobacterium tuberculosis during inhibition of respiration","volume":"190","author":"Sohaskey","year":"2008","journal-title":"J. Bacteriol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/fml.2008.290.issue-2","article-title":"Differences in nitrate reduction between Mycobacterium tuberculosis and Mycobacterium bovis are due to differential expression of both narGHJI and narK2","volume":"290","author":"Sohaskey","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"B54","doi-asserted-by":"publisher","first-page":"7247","DOI":"10.1128\/JB.185.24.7247-7256.2003","article-title":"Role of narK2X and narGHJI in hypoxic upregulation of nitrate reduction by Mycobacterium tuberculosis","volume":"185","author":"Sohaskey","year":"2003","journal-title":"J. Bacteriol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1093\/nar\/gks1203","article-title":"Competition between the GlnR and PhoP regulators for the glnA and amtB promoters in Streptomyces coelicolor","volume":"41","author":"Sola-Landa","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02273","article-title":"Mycobacterium abscessus and beta-Lactams: Emerging Insights and Potential Opportunities","volume":"9","author":"Story-Roller","year":"2018","journal-title":"Front. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5051","DOI":"10.1074\/jbc.RA120.012859","article-title":"A recently evolved diflavin-containing monomeric nitrate reductase is responsible for highly efficient bacterial nitrate assimilation","volume":"295","author":"Tan","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"14","DOI":"10.4161\/psb.5.1.10173","article-title":"Siroheme: an essential component for life on earth","volume":"5","author":"Tripathy","year":"2010","journal-title":"Plant Signal Behav."},{"key":"B59","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/nmeth996","article-title":"Recombineering in mycobacterium tuberculosis","volume":"4","author":"van Kessel","year":"2007","journal-title":"Nat. Methods"},{"key":"B60","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/nrmicro2014","article-title":"Recombineering mycobacteria and their phages","volume":"6","author":"van Kessel","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.909904","article-title":"Commonalities of mycobacterium tuberculosis transcriptomes in response to defined persisting macrophage stresses","volume":"13","author":"Vilcheze","year":"2022","journal-title":"Front. Immunol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1084\/jem.20030205","article-title":"Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program","volume":"198","author":"Voskuil","year":"2003","journal-title":"J. Exp. Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.tube.2004.02.003","article-title":"Mycobacterium tuberculosis gene expression during adaptation to stationary phase and low-oxygen dormancy","volume":"84","author":"Voskuil","year":"2004","journal-title":"Tuberculosis (Edinb)"},{"key":"B64","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1054\/tuld.1998.0015","article-title":"Nitrate reduction as a marker for hypoxic shiftdown of Mycobacterium tuberculosis","volume":"79","author":"Wayne","year":"1998","journal-title":"Tuber Lung Dis."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0172831","article-title":"Comparative genome analyses of mycobacteria give better insights into their evolution","volume":"12","author":"Wee","year":"2017","journal-title":"PloS One"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1111\/mmi.13091","article-title":"Deciphering the metabolic response of Mycobacterium tuberculosis to nitrogen stress","volume":"97","author":"Williams","year":"2015","journal-title":"Mol. Microbiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1172\/JCI0213870","article-title":"Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients","volume":"109","author":"Worlitzsch","year":"2002","journal-title":"J. Clin. Invest."},{"key":"B68","doi-asserted-by":"publisher","first-page":"27326","DOI":"10.1038\/srep27326","article-title":"Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"B69","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/nchembio.2259","article-title":"Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence","volume":"13","author":"Zheng","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/mmi.14252","article-title":"The developmental regulator MtrA binds GlnR boxes and represses nitrogen metabolism genes in Streptomyces coelicolor","volume":"112","author":"Zhu","year":"2019","journal-title":"Mol. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1411333\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T04:41:44Z","timestamp":1716525704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1411333\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,24]]},"references-count":70,"alternative-id":["10.3389\/fcimb.2024.1411333"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2024.1411333","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,24]]},"article-number":"1411333"}}