title: The Mycobacterium tuberculosis β-oxidation genes echA5 and fadB3 are dispensable for growth in vitro and in vivo.
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.
authors.affiliation: Centre for Molecular Medicine & Infection, Department of Medicine, Flowers Building, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Kerstin J
authors.initials: KJ
authors.lastname: Williams
authors.forename: Helena I
authors.initials: HI
authors.lastname: Boshoff
authors.forename: Nitya
authors.initials: N
authors.lastname: Krishnan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gonzales
authors.forename: Dirk
authors.initials: D
authors.lastname: Schnappinger
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robertson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003470:Culture Media; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D010084:Oxidation-Reduction; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D016207:Cytokines; C113704:resuscitation-promoting factor, bacteria