Cell Envelope Proteomics of Mycobacteria

Abstract

The World Health Organization (WHO) estimates that Mycobacterium tuberculosis, the most pathogenic mycobacterium species to humans, has infected up to a quarter of the world's population, with the occurrence of multidrug-resistant strains on the rise. Research into the detailed composition of the cell envelope proteome in mycobacteria over the last 20 years has formed a key part of the efforts to understand host−pathogen interactions and to control the current tuberculosis epidemic. This is due to the great importance of the cell envelope proteome during infection and during the development of antibiotic resistance as well as the search of surface-exposed proteins that could be targeted by therapeutics and vaccines. A variety of experimental approaches and mycobacterial species have been used in proteomic studies thus far. Here we provide for the first time an extensive summary of the different approaches to isolate the mycobacterial cell envelope, highlight some of the limitations of the studies performed thus far, and comment on how the recent advances in membrane proteomics in other fields might be translated into the field of mycobacteria to provide deeper coverage.

Chemical Proteomics Strategies for Analyzing Protein Lipidation Reveal the Bacterial O-Mycoloylome

“…Although mycobacteria lack strict orthologs of Cg Cmt1, they possess multiple structurally similar mycoloyltransferases with relatively high substrate tolerance that should be explored for protein O -mycoloylation activity. The tools reported herein will facilitate efforts to discover and characterize O -mycoloylated proteins in additional organisms and, along with other emerging strategies for studying cell envelope proteins in the Corynebacterineae , , are expected to contribute to an improved understanding of the mycomembrane proteome. Our tools may also be useful for comparing and contrasting the scope and functional roles of O -mycoloylation and N -acyl- S -diacyl-glycerylation, the latter of which generates lipoproteins that associate with the cell envelope in corynebacteria and mycobacteria. , …”

“…Despite intense interest in characterizing the proteomic composition of the mycomembrane toward the discovery of novel drug targets, − the extent to which protein O -mycoloylation occurs beyond a few mycomembrane porins in Cg is unknown, and there remains little information about the roles of O -mycoloylation in protein structure, localization, and function. These knowledge gaps underscore the limited ability of traditional methods to analyze protein–lipid PTMs on the whole-proteome scale .…”

Nocardia seriolae mediates liver granulomatous chronic inflammation in Micropterus salmoides through pyroptosis

“…Mycobacterium also has other unique components, such as lipoarabinomannan and mycobacterial factor trehalose-6,6-dimethyl (Hermann et al, 2020), which can activate PRR of cells and mediate pyroptosis. Cell pyroptosis, a type of programmed cell death, is part of the innate immune system that is used to resist tissue damage and invasion of external pathogens (Gong et al, 2020).…”

“…Mycobacterial cell wall structure is relatively special because it has a large number of branched mycolic acids surrounding the outside of the peptidoglycan layer, which can resist the external acidic environment. Mycobacterium also has other unique components, such as lipoarabinomannan and mycobacterial factor trehalose‐6,6‐dimethyl (Hermann et al, 2020), which can activate PRR of cells and mediate pyroptosis. Cell pyroptosis, a type of programmed cell death, is part of the innate immune system that is used to resist tissue damage and invasion of external pathogens (Gong et al, 2020).…”

S16 and T18 mannosylation sites of LppX are not essential for its activity in phthiocerol dimycocerosates localization at the surface of Mycobacterium tuberculosis

“…In our work, when expressed in M. smegmatis, LppX-tb was detected in the membrane fraction. In M. tuberculosis and M. bovis LppX-tb and its ortholog were found associated to the outermost layers of the cells that is the cell wall [27][28][29] and the cell surface [27]. In these mycobacteria, the cell wall is surrounded by a capsular layer [22]).…”