{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T22:14:59Z","timestamp":1782166499103,"version":"3.54.5"},"reference-count":82,"publisher":"Microbiology Society","issue":"11","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009053","name":"The Wellcome Trust DBT India Alliance","doi-asserted-by":"crossref","award":["IA\/S19\/2\/504646"],"award-info":[{"award-number":["IA\/S19\/2\/504646"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,30]]},"abstract":"<jats:p>Toxin\u2013antitoxin (TA) systems are abundantly present in the genomes of various bacterial pathogens. TA systems have been implicated in either plasmid maintenance or protection against phage infection, stress adaptation or disease pathogenesis. The genome of <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.10886\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> encodes for more than 90 TA systems and 4 of these belong to the type IV subfamily (MenAT family). The toxins and antitoxins belonging to type IV TA systems share sequence homology with the AbiEii family of nucleotidyl transferases and the AbiEi family of putative transcriptional regulators, respectively. Here, we have performed experiments to understand the role of MenT2, a toxin from the type IV TA system, in mycobacterial physiology and disease pathogenesis. The ectopic expression of MenT2 using inducible vectors does not inhibit bacterial growth in liquid cultures. Bioinformatic and molecular modelling analysis suggested that the <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.10886\" xlink:type=\"simple\">M. tuberculosis<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> genome has an alternative start site upstream of the annotated <jats:italic>menT2<\/jats:italic> gene. The overexpression of the reannotated MenT2 resulted in moderate growth inhibition of <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.6403\" xlink:type=\"simple\">Mycobacterium smegmatis<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic>. We show that both <jats:italic>menT2<\/jats:italic> and <jats:italic>menA2<\/jats:italic> transcript levels are increased when <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.10886\" xlink:type=\"simple\">M. tuberculosis<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> is exposed to nitrosative stress, <jats:italic>in vitro<\/jats:italic>. When compared to the survival of the wild-type and the complemented strain, the \u0394<jats:italic>menT2<\/jats:italic> mutant strain of <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.10886\" xlink:type=\"simple\">M. tuberculosis<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> was more resistant to being killed by nitrosative stress. However, the survival of both the \u0394<jats:italic>menT2<\/jats:italic> mutant and the wild-type strain was similar in macrophages and when exposed to other stress conditions. Here, we show that MenT2 is required for the establishment of disease in guinea pigs. Gross pathology and histopathology analysis of lung tissues from guinea pigs infected with the <jats:italic>\u2206menT2<\/jats:italic> strain revealed significantly reduced tissue damage and inflammation. In summary, these results provide new insights into the role of MenT2 in mycobacterial pathogenesis.<\/jats:p>","DOI":"10.1099\/mic.0.001246","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T17:20:39Z","timestamp":1667841639000},"source":"Crossref","is-referenced-by-count":13,"title":["Disruption of MenT2 toxin impairs the growth of Mycobacterium tuberculosis in guinea pigs"],"prefix":"10.1099","volume":"168","author":[{"given":"Tannu Priya","family":"Gosain","sequence":"first","affiliation":[{"name":"Infection and Immunology Group, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad Gurugram Expressway, Faridabad-121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Singh","sequence":"additional","affiliation":[{"name":"Infection and Immunology Group, Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad Gurugram Expressway, Faridabad-121001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charandeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Structural Biology Laboratory, G. 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