Unveiling phenotypic differences among the genetically conserved Mycobacterium tuberculosis complex: Characterization of proteomes and post-translational modifications

Abstract

Members of the genetically conserved Mycobacterium tuberculosis complex (MTBC) exhibit vast discrepancies in clinical outcome and epidemiological behaviour. Bacterial factors that contribute to these phenotypic variabilities remain elusive. We hypothesize that qualitative and quantitative differences in the abundance of proteins and their post-translational modifications (PTMs) may contribute to MTBC phenotypic diversity. The study analyzed the proteomic and PTM profiles (acetylation and glycosylation) among members of the MTBC using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Comparative proteomic analysis of the MTBC lineages revealed significantly different abundances of proteins involved in virulence, growth and bioenergetics. The PTM study provides the first report on O-acetylation and N-glycosylation of MTBC proteins. The study presents a comprehensive proteomic and PTM map of MTBC and demonstrated the presence of significant differences among different lineages. These new discoveries will enable a better understanding of the pathogen with new potential for identification of novel drug targets and vaccine candidates, as well as efficient diagnostics for TB disease.