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The Mycobacterium tuberculosis β-oxidation genes echA5 and fadB3 are dispensable for growth in vitro and in vivo.

TitleThe Mycobacterium tuberculosis β-oxidation genes echA5 and fadB3 are dispensable for growth in vitro and in vivo.
Publication TypeJournal Article
Year of Publication2011
AuthorsWilliams KJ, Boshoff HI, Krishnan N, Gonzales J, Schnappinger D, Robertson BD
JournalTuberculosis (Edinb)
Volume91
Issue6
Pagination549-55
Date Published2011 Nov
ISSN1873-281X
KeywordsAnimals, Bacterial Proteins, Culture Media, Cytokines, Gene Deletion, Gene Expression Regulation, Bacterial, Humans, Macrophages, Mice, Mycobacterium tuberculosis, Oxidation-Reduction, Tuberculosis, Pulmonary
Abstract

There are several lines of evidence pointing towards the importance of β-oxidation in host survival of Mycobacterium tuberculosis including enormous gene redundancy for this process; approximately 100 genes are annotated as β-oxidation genes for the five biochemical reactions that break down fatty acids into acetyl-CoA. Although most of these genes are predicted to be non-essential, two of the genes (echA5 and fadB3) are annotated as essential for growth in vitro, and therefore could be considered as putative drug targets. However, here we report the construction of echA5 and fadB3 null mutants confirming they are non-essential. No significant difference in growth between the mutant and parent strains was observed in either standard Middlebrook medium or in minimal medium supplemented with various carbon sources. Macrophage survival and mouse infection studies also showed no significant difference between the mutant and parent strains. Therefore, we conclude that these genes are dispensable for growth in vitro and in vivo.

DOI10.1016/j.tube.2011.06.006
Alternate JournalTuberculosis (Edinb)
PubMed ID21764638
PubMed Central IDPMC3220763
Grant List077381 / / Wellcome Trust / United Kingdom
/ / Intramural NIH HHS / United States

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