{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:42:44Z","timestamp":1782351764928,"version":"3.54.5"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1024038"],"award-info":[{"award-number":["OPP1024038"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2020,10,28]]},"abstract":"<jats:p>\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            is a major global human pathogen, and new drugs and new drug targets are urgently required. Cell wall biosynthesis is a major target of current tuberculosis drugs and of new agents under development. Several new classes of molecules appear to have the same target, MmpL3, which is involved in the export and synthesis of the mycobacterial cell wall. However, there is still debate over whether MmpL3 is the primary or only target for these classes. We wanted to confirm the mechanism of resistance for one series. We identified mutations in MmpL3 which led to resistance to the spiral amine series. High-level resistance to these compounds and two other series was conferred by multiple mutations in the same protein (MmpL3). These mutations did not reduce growth rate in culture. These results support the hypothesis that MmpL3 is the primary mechanism of resistance and likely target for these pharmacophores.\n          <\/jats:p>","DOI":"10.1128\/msphere.00985-20","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T13:28:56Z","timestamp":1602682136000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Multiple Mutations in Mycobacterium tuberculosis MmpL3 Increase Resistance to MmpL3 Inhibitors"],"prefix":"10.1128","volume":"5","author":[{"given":"Matthew B.","family":"McNeil","sequence":"first","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"O\u2019Malley","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Dennison","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine D.","family":"Shelton","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Sunde","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7507-0423","authenticated-orcid":false,"given":"Tanya","family":"Parish","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"},{"name":"Seattle Children\u2019s Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Global tuberculosis report 2019","author":"World Health Organization","year":"2020","unstructured":"World Health Organization. 2020. 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