{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:26:58Z","timestamp":1791563218534,"version":"4.3.4"},"reference-count":100,"publisher":"Microbiology Society","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"\n \n \n Mycobacterium tuberculosis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> is a known human pathogen that causes the airborne infectious disease tuberculosis (TB). Every year TB infects millions of people worldwide. The emergence of multi-drug resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) \n \n M. tuberculosis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> strains against the first- and second-line anti-TB drugs has created an urgent need for the development and implementation of new drug strategies. In this study, the complete genomes of 174 strains of \n \n M. tuberculosis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> are analysed to understand the evolution of molecular drug target (MDT) genes. Phylogenomic placements of \n \n M. tuberculosis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> strains depicted close association and temporal clustering. Selection pressure analysis by deducing the ratio of non-synonymous to synonymous substitution rates (dN\/dS<\/jats:italic>) in 51 MDT genes of the 174 \n \n M<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>. \n \n tuberculosis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic> strains led to categorizing these genes into diversifying (D, dN\/dS<\/jats:italic>>0.70), moderately diversifying (MD, dN\/dS<\/jats:italic>=0.35\u20130.70) and stabilized (S, dN\/dS<\/jats:italic><0.35) genes. The genes rpsL, gidB, pncA<\/jats:italic> and ahpC<\/jats:italic> were identified as diversifying, and Rv0488, kasA, ndh, ethR, ethA<\/jats:italic>, embR<\/jats:italic> and ddn<\/jats:italic> were identified as stabilized genes. Furthermore, sequence similarity networks were drawn that supported these divisions. In the multiple sequence alignments of diversifying and stabilized proteins, previously reported resistance mutations were checked to predict sensitive and resistant strains of \n \n M. tuberculosis<\/jats:ext-link>\n <\/jats:named-content>\n <\/jats:italic>. Finally, to delineate the potential of stabilized or least diversified genes\/proteins as anti-TB drug targets, protein\u2013protein interactions of MDT proteins with human proteins were analysed. We predict that kasA<\/jats:italic> (dN\/dS<\/jats:italic>=0.29), a stabilized gene that encodes the most host-interacting protein, KasA, should serve as a potential drug target for the treatment of TB.<\/jats:p>","DOI":"10.1099\/mgen.0.000542","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T15:16:11Z","timestamp":1616426171000},"source":"Crossref","is-referenced-by-count":10,"title":["Genome analyses of 174 strains of Mycobacterium tuberculosis provide insight into the evolution of drug resistance and reveal potential drug targets"],"prefix":"10.1099","volume":"7","author":[{"given":"Helianthous","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India"},{"name":"Molecular Biology and Genomics Research Laboratory, Ramjas College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shekhar","family":"Nagar","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Vohra","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India"},{"name":"Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhanshu","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Jamia Millia Islamia, Okhla, New Delhi 110025, India"},{"name":"Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of 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