Metabolic profile of Mycobacterium smegmatis reveals Mce4 proteins are relevant for cell wall lipid homeostasis

MARÍA DE LA PAZ SANTANGELO; ADAM HEUBERGER; FEDERICO BLANCO; MARINA ANDREA FORRELLAD; CATALINA TAIBO; LAURA INÉS KLEPP; JULIA SABIO Y GARCÍA; PABLO NIKEL; MARY JACKSON; FABIANA BIGI

METABOLOMICS

SPRINGER

Lugar: Berlin; Año: 2016 vol. 12 p. 97 - 108

1573-3882

Introduction The Mce proteins are encoded in a variablenumber of operons (from one to eight) in all Mycobacteriumspecies. A role in the transport of host andmycobacterial lipids has been demonstrated for some Mceproteins in the pathogen Mycobacterium tuberculosis butlittle is known about these proteins in Mycobacteriumsmegmatis, a soil dweller species.Objective To investigate the role of Mce proteins in M.smegmatis.Method We used a non-targeted GC?MS approach todefine the metabolic profiles of knockout mutants in mceoperons of M. smegmatis. Metabolomic analysis wascomplemented with thin layer chromatography and transcriptionalstudies.Result We demonstrated that the lack of Mce4 proteinsalters the primary carbon metabolism of M. smegmatis byreducing the content of fatty acids and increasing theaccumulation of two stress-related compounds, glutamate/glutamine and triacyl glycerol (TAG). We also provideevidence supporting that the accumulation of TAG in aDmce4 mutant depends on the bacterial redox state.Conclusion These results, together with the finding that thecell surface of the Dmce4 mutant is significantly altered,support a role for Mce4 in maintaining the cell wall lipidsarchitecture of M. smegmatis, which, when altered, inducesa redox imbalance that results in the accumulation of thestress-related compounds.