{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:31:48Z","timestamp":1781105508607,"version":"3.54.1"},"reference-count":112,"publisher":"National Academy of Sciences","issue":"29","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI106872"],"award-info":[{"award-number":["AI106872"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"<jats:p>\n                    Phagosomal lysis is essential for mycobacterial infection of macrophages. Acetylation is a protein modification mediated enzymatically by N-acetyltransferases (NATs) that impacts bacterial pathogenesis and physiology. To identify NATs required for lytic activity, we leveraged\n                    <jats:italic toggle=\"yes\">Mycobacterium marinum,<\/jats:italic>\n                    a nontubercular pathogen and a model for\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis. M. marinum<\/jats:italic>\n                    hemolysis is a proxy for phagolytic activity. We generated\n                    <jats:italic toggle=\"yes\">M. marinum<\/jats:italic>\n                    strains with deletions in conserved NAT genes and screened for hemolytic activity. Several conserved lysine acetyltransferases (KATs) contributed to hemolysis, which is mediated by the ESX-1 secretion system and by the virulence lipid phthiocerol dimycocerosate (PDIM). Using thin-layer chromatography, we found that MbtK, a conserved acyl-transferase required for mycobactin siderophore synthesis and virulence, was required for PDIM and phenolic glycolipid (PGL) production. Exogenous addition of sodium propionate or Mycobactin J restored PDIM\/PGL production in the \u0394\n                    <jats:italic toggle=\"yes\">mbtK<\/jats:italic>\n                    strain. The \u0394\n                    <jats:italic toggle=\"yes\">mbtK M. marinum<\/jats:italic>\n                    strain was attenuated in macrophage and\n                    <jats:italic toggle=\"yes\">Galleria mellonella<\/jats:italic>\n                    infection models. Constitutive expression of either\n                    <jats:italic toggle=\"yes\">eis<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">papA5,<\/jats:italic>\n                    which encode a KAT required for aminoglycoside resistance and a PDIM\/PGL biosynthetic enzyme, rescued PDIM\/PGL production, and virulence of the \u2206\n                    <jats:italic toggle=\"yes\">mbtK<\/jats:italic>\n                    strain. Eis N-terminally acetylated PapA5 in vitro, providing a plausible mechanism for restored lipid production. Overall, our study establishes connections between the MbtK and Eis NATs, and between iron uptake and PDIM and PGL synthesis in\n                    <jats:italic toggle=\"yes\">M. marinum<\/jats:italic>\n                    . Our findings underscore the multifunctional nature of mycobacterial NATs and their connection to key virulence pathways.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2502577122","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T17:37:10Z","timestamp":1752860230000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["N\n                    <i>-<\/i>\n                    acetyltransferases required for iron uptake and aminoglycoside resistance promote virulence lipid production in\n                    <i>Mycobacterium marinum<\/i>"],"prefix":"10.1073","volume":"122","author":[{"given":"Bradley S.","family":"Jones","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame","place":["Notre Dame"]},{"name":"Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Pareek","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4354-0309","authenticated-orcid":false,"given":"Simon D.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8632-1339","authenticated-orcid":false,"given":"Camille","family":"Syska","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Galfano","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-5277","authenticated-orcid":false,"given":"Matthew M.","family":"Champion","sequence":"additional","affiliation":[{"name":"Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame"]},{"name":"Department of Chemistry and Biochemistry, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6733-596X","authenticated-orcid":false,"given":"Patricia A.","family":"Champion","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Notre Dame","place":["Notre Dame"]},{"name":"Eck Institute for Global Health, University of Notre Dame","place":["Notre Dame"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b01269"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297909070062"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6658"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110148297"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1183147"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2016.06.007"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406239101"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5383"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2386"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.06.014"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0116-z"},{"key":"e_1_3_4_12_2","first-page":"457","article-title":"Tuberculosis etiology","volume":"7","author":"Koch R.","year":"1884","unstructured":"R. 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