{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:21:19Z","timestamp":1782454879566,"version":"3.54.5"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T00:00:00Z","timestamp":1657497600000},"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. Microbiol."],"abstract":"<jats:p>The increasing incidence of drug-resistant tuberculosis is still an emergency for global public health and a major obstacle to tuberculosis treatment. Therefore, deciphering the novel mechanisms of <jats:italic>mycobacterial<\/jats:italic> antibiotic resistance is crucial for combatting the rapid emergence of drug-resistant strains. In this study, we identified an unexpected role of <jats:italic>Mycobacterium smegmatis<\/jats:italic> GntR family transcriptional regulator MSMEG_5174 and its homologous gene <jats:italic>Mycobacterium tuberculosis<\/jats:italic> Rv1152 in aminoglycoside antibiotic resistance. Deficiency of MSMEG_5174 rendered <jats:italic>Mycobacterium smegmatis<\/jats:italic> highly resistant to aminoglycoside antibiotic treatment, and ectopic expression of Rv1152 in MSMEG_5174 mutants restored antibiotic-induced bacterial killing. We further demonstrated that MSMEG_5174 negatively regulates the expression of purine metabolism-related genes and the accumulation of purine metabolites. Moreover, overexpression of xanthine dehydrogenase MSMEG_0871 or xanthine treatment elicited a significant decrease in aminoglycoside antibiotic lethality for <jats:italic>Mycobacterium smegmatis<\/jats:italic>. Together, our findings revealed MSMEG_5174 as a metabolic regulator and hint toward unexplored crosstalk between purine metabolism and antibiotic resistance.<\/jats:p>","DOI":"10.3389\/fmicb.2022.919538","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T06:02:17Z","timestamp":1657519337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Deficiency of GntR Family Regulator MSMEG_5174 Promotes Mycobacterium smegmatis Resistance to Aminoglycosides via Manipulating Purine Metabolism"],"prefix":"10.3389","volume":"13","author":[{"given":"Wanyan","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengzhang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitang","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huasong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature10069","article-title":"Metabolite-enabled eradication of bacterial persisters by aminoglycosides.","volume":"473","author":"Allison","year":"2011","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5470","DOI":"10.1128\/jb.172.9.5470-5476.1990","article-title":"Nucleotide sequence of the gene encoding the repressor for the histidine utilization genes of Pseudomonas putida.","volume":"172","author":"Allison","year":"1990","journal-title":"J. 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