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However, environmental factors governing mycobacterial ILI formation and degradation remain poorly understood. Herein, we demonstrated that in the absence of host cells, carbon excess and nitrogen starvation promote TAG accumulation in the form of ILI in <jats:italic>M. smegmatis<\/jats:italic> and <jats:italic>M. abscessus<\/jats:italic>, used as surrogate species of <jats:italic>M. tb<\/jats:italic>. Based on these findings, we developed a simple and reversible <jats:italic>in vitro<\/jats:italic> model to regulate ILI biosynthesis and hydrolysis in mycobacteria. We also showed that TAG formation is <jats:italic>tgs1<\/jats:italic> dependent and that lipolytic enzymes mediate TAG breakdown. Moreover, we confirmed that the nitrogen-deprived and ILI-rich phenotype was associated with an increased tolerance towards several drugs used for treating mycobacterial infections. Importantly, we showed that the presence of ILI substantially enhanced the bacterial burden and granuloma abundance in zebrafish embryos infected with lipid-rich <jats:italic>M. abscessus<\/jats:italic> as compared to embryos infected with lipid-poor <jats:italic>M. abscessus<\/jats:italic>, suggesting that ILI are actively contributing to mycobacterial virulence and pathogenesis.<\/jats:p>","DOI":"10.1038\/s41598-019-45164-5","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T10:02:40Z","timestamp":1560765760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria"],"prefix":"10.1038","volume":"9","author":[{"given":"Pierre","family":"Santucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-5270","authenticated-orcid":false,"given":"Matt D.","family":"Johansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Point","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Poncin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertus","family":"Viljoen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0864-8314","authenticated-orcid":false,"given":"Jean-Fran\u00e7ois","family":"Cavalier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6604-4458","authenticated-orcid":false,"given":"Laurent","family":"Kremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7478-300X","authenticated-orcid":false,"given":"St\u00e9phane","family":"Canaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,17]]},"reference":[{"key":"45164_CR1","unstructured":"WHO. 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