A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism

Unlike most bacteria, mycobacteria rely on the multi-domain enzyme eukaryote-like fatty acid synthase I (FAS I) to make fatty acids de novo. These metabolites are precursors of the biosynthesis of most of the lipids present both in the complex mycobacteria cell wall and in the storage lipids ins...

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Autores principales: Cabruja, Matías Ezequiel, Mondino, Sonia Soledad, Tsai, Yi-Ting, Lara, María Julia, Gramajo, Hugo Cesar, Gago, Gabriela
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: Royal Society 2020
Materias:
Microbiology
Fatty Acid Synthase Type I
Tuberculosis
Mycolic Acids
Acceso en línea:http://hdl.handle.net/2133/19535
http://hdl.handle.net/2133/19535
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-19535
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Microbiology
Fatty Acid Synthase Type I
Tuberculosis
Mycolic Acids
spellingShingle Microbiology
Fatty Acid Synthase Type I
Tuberculosis
Mycolic Acids
Cabruja, Matías Ezequiel
Mondino, Sonia Soledad
Tsai, Yi-Ting
Lara, María Julia
Gramajo, Hugo Cesar
Gago, Gabriela
A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
topic_facet Microbiology
Fatty Acid Synthase Type I
Tuberculosis
Mycolic Acids
description Unlike most bacteria, mycobacteria rely on the multi-domain enzyme eukaryote-like fatty acid synthase I (FAS I) to make fatty acids de novo. These metabolites are precursors of the biosynthesis of most of the lipids present both in the complex mycobacteria cell wall and in the storage lipids inside the cell. In order to study the role of the type I FAS system in Mycobacterium lipid metabolism in vivo, we constructed a conditional mutant in the fas-acpS operon of Mycobacterium smegmatis and analysed in detail the impact of reduced de novo fatty acid biosynthesis on the global architecture of the cell envelope. As expected, the mutant exhibited growth defect in the non-permissive condition that correlated well with the lower expression of fas-acpS and the concomitant reduction of FAS I, confirming that FAS I is essential for survival. The reduction observed in FAS I provoked an accumulation of its substrates, acetyl-CoA and malonyl-CoA, and a strong reduction of C12 to C18 acyl-CoAs, but not of long-chain acylCoAs (C19 to C24). The most intriguing result was the ability of the mutant to keep synthesizing mycolic acids when fatty acid biosynthesis was impaired. A detailed comparative lipidomic analysis showed that although reduced FAS I levels had a strong impact on fatty acid and phospholipid biosynthesis, mycolic acids were still being synthesized in the mutant, although with a different relative species distribution. However, when triacylglycerol degradation was inhibited, mycolic acid biosynthesis was significantly reduced, suggesting that storage lipids could be an intracellular reservoir of fatty acids for the biosynthesis of complex lipids in mycobacteria. Understanding the interaction between FAS I and the metabolic pathways that rely on FAS I products is a key step to better understand how lipid homeostasis is regulated in this microorganism and how this regulation could play a role during infection in pathogenic mycobacteria.
format article
artículo
publishedVersion
author Cabruja, Matías Ezequiel
Mondino, Sonia Soledad
Tsai, Yi-Ting
Lara, María Julia
Gramajo, Hugo Cesar
Gago, Gabriela
author_facet Cabruja, Matías Ezequiel
Mondino, Sonia Soledad
Tsai, Yi-Ting
Lara, María Julia
Gramajo, Hugo Cesar
Gago, Gabriela
author_sort Cabruja, Matías Ezequiel
title A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
title_short A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
title_full A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
title_fullStr A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
title_full_unstemmed A conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
title_sort conditional mutant of the fatty acid synthase unveils unexpected cross talks in mycobacterial lipid metabolism
publisher Royal Society
publishDate 2020
url http://hdl.handle.net/2133/19535
http://hdl.handle.net/2133/19535
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