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Long-chain acyl-CoA synthetases (ACSLs) are key host-cell enzymes that convert fatty acids (FA) into acyl-CoA for use in metabolic pathways. Here, we show that the complete host ACSL family [ACSL1 and ACSL3\u20136] translocates into the <jats:italic>Ct<\/jats:italic> membrane-bound vacuole, termed inclusion and remains associated with membranes of metabolically active forms of <jats:italic>Ct<\/jats:italic> throughout development. We discovered that three different pharmacologic inhibitors of ACSL activity independently impede <jats:italic>Ct<\/jats:italic> growth in a dose-dependent fashion. Using an FA competition assay, host ACSLs were found to activate <jats:italic>Ct<\/jats:italic> branched-chain FAs, suggesting that one function of the ACSLs is to activate <jats:italic>Ct<\/jats:italic> FAs and host FAs (recruited from the cytoplasm) within the inclusion. Because the ACSL inhibitors can deplete lipid droplets (LD), we used a cell line where LD synthesis was switched off to evaluate whether LD deficiency affects <jats:italic>Ct<\/jats:italic> growth. In these cells, we found no effect on growth or on translocation of ACSLs into the inclusion. Our findings support an essential role for ACSL activation of host-cell and bacterial FAs within the inclusion to promote <jats:italic>Ct<\/jats:italic> growth and development, independent of LDs.<\/jats:p>","DOI":"10.1038\/srep23148","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T10:07:36Z","timestamp":1458295656000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Chlamydia trachomatis growth and development requires the activity of host Long-chain Acyl-CoA Synthetases (ACSLs)"],"prefix":"10.1038","volume":"6","author":[{"given":"Maria A.","family":"Recuero-Checa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Gaydos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,18]]},"reference":[{"key":"BFsrep23148_CR1","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1136\/sti.2007.028142","volume":"83","author":"DA Lewis","year":"2007","unstructured":"Lewis, D. 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