{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:47:37Z","timestamp":1787496457081,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,29]],"date-time":"2016-10-29T00:00:00Z","timestamp":1477699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Community's Seventh Framework Programme","award":["Grant 260872"],"award-info":[{"award-number":["Grant 260872"]}]},{"name":"GSouth African Medical Research Council"},{"name":"National Research Foundation of South Africa"},{"name":"Senior International Research Scholar's grant","award":["55007649"],"award-info":[{"award-number":["55007649"]}]},{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Commission Marie Curie Fellowship","award":["PIEF-GA-2012-327219"],"award-info":[{"award-number":["PIEF-GA-2012-327219"]}]},{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"Summary<\/jats:title>\n \n There is an urgent need to discover new anti\u2010tubercular agents with novel mechanisms of action in order to tackle the scourge of drug\u2010resistant tuberculosis. Here, we report the identification of such a molecule \u2013 an AminoPYrimidine\u2010Sulfonamide (\n APYS1<\/jats:bold>\n ) that has potent, bactericidal activity against\n M. tuberculosis<\/jats:italic>\n . Mutations in\n APYS1<\/jats:bold>\n \u2010resistant\n M. tuberculosis<\/jats:italic>\n mapped exclusively to\n wag31<\/jats:italic>\n , a gene that encodes a scaffolding protein thought to orchestrate cell elongation. Recombineering confirmed that a Gln201Arg mutation in Wag31 was sufficient to cause resistance to\n APYS1<\/jats:bold>\n , however, neither overexpression nor conditional depletion of\n wag31<\/jats:italic>\n impacted\n M. tuberculosis<\/jats:italic>\n susceptibility to this compound. In contrast, expression of the wildtype allele of\n wag31<\/jats:italic>\n in\n APYS1<\/jats:bold>\n \u2010resistant\n M. tuberculosis<\/jats:italic>\n was dominant and restored susceptibility to\n APYS1<\/jats:bold>\n to wildtype levels. Time\u2010lapse imaging and scanning electron microscopy revealed that\n APYS1<\/jats:bold>\n caused gross malformation of the old pole of\n M. tuberculosis<\/jats:italic>\n , with eventual lysis. These effects resembled the morphological changes observed following transcriptional silencing of\n wag31<\/jats:italic>\n in\n M. tuberculosis<\/jats:italic>\n . These data show that Wag31 is likely not the direct target of\n APYS1<\/jats:bold>\n , but the striking phenotypic similarity between\n APYS1<\/jats:bold>\n exposure and genetic depletion of Wag31 in\n M. tuberculosis<\/jats:italic>\n suggests that\n APYS1<\/jats:bold>\n might indirectly affect Wag31 through an as yet unknown mechanism.\n <\/jats:p>","DOI":"10.1111\/mmi.13535","type":"journal-article","created":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T04:48:53Z","timestamp":1475038133000},"page":"13-25","source":"Crossref","is-referenced-by-count":32,"title":["Identification of aminopyrimidine\u2010sulfonamides as potent modulators of Wag31\u2010mediated cell elongation in mycobacteria"],"prefix":"10.1111","volume":"103","author":[{"given":"Vinayak","family":"Singh","sequence":"first","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine & Department of Pathology University of Cape Town, MRC\/NHLS\/UCT Molecular Mycobacteriology Research Unit & DST\/NRF Centre of Excellence for Biomedical TB Research South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Dhar","sequence":"additional","affiliation":[{"name":"Microbiology and Microsystems Global Health Institute, Ecole Polytechnique Federale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Pat\u00f3","sequence":"additional","affiliation":[{"name":"Vichem Chemie Research Ltd, Herman Otto u. 15 Budapest 1022 Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle S.","family":"Kolly","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis, Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Kordul\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Now at: 1st Department of Internal Medicine University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Forbak","sequence":"additional","affiliation":[{"name":"Now at: 1st Department of Internal Medicine University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna C.","family":"Evans","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine & Department of Pathology University of Cape Town, MRC\/NHLS\/UCT Molecular Mycobacteriology Research Unit & DST\/NRF Centre of Excellence for Biomedical TB Research South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Sz\u00e9kely","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis, Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rybniker","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis, Global Health Institute, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne Lausanne Switzerland"},{"name":"Now at: 1st Department of Internal Medicine University of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Pal\u010dekov\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Department of Biochemistry Comenius University in Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falia","family":"Zemanov\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Department of Biochemistry Comenius University in Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Santi","sequence":"additional","affiliation":[{"name":"Microbiology and Microsystems Global Health Institute, Ecole Polytechnique Federale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Signorino\u2010Gelo","sequence":"additional","affiliation":[{"name":"Microbiology and Microsystems Global Health Institute, Ecole Polytechnique Federale de Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Departamento de Microbiolog\u00eda, Facultad de Medicina Universidad de Zaragoza, and Fundaci\u00f3n ARAID, Zaragoza, Spain; 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