Metabolic profile ofMycobacterium smegmatisreveals Mce4 proteins are relevant for cell wall lipid homeostasis

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

METABOLOMICS

SPRINGER

Lugar: Berlin; Año: 2016 vol. 12 p. 1 - 11

1573-3882

Introduction The Mce proteins are encoded in a variablenumber of operons (from one to eight) in allMycobacterium species. A role in the transport of host andmycobacterial lipids has been demonstrated for some Mceproteins in the pathogenMycobacterium tuberculosisbutlittle is known about these proteins in Mycobacteriumsmegmatis, a soil dweller species.ObjectiveTo investigate the role of Mce proteins inM.smegmatis.MethodWe used a non-targeted GC?MS approach todefine the metabolic profiles of knockout mutants inmceoperons of M. smegmatis. Metabolomic analysis wascomplemented with thin layer chromatography and transcriptional studies.ResultWe demonstrated that the lack of Mce4 proteinsalters the primary carbon metabolism ofM. smegmatisbyreducing 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 aDmce4mutant depends on the bacterial redox state.ConclusionThese results, together with the finding that thecell surface of theDmce4mutant is significantly altered,support a role for Mce4 in maintaining the cell wall lipidsarchitecture ofM. smegmatis, which, when altered, inducesa redox imbalance that results in the accumulation of thestress-related compounds.