Proteomics of bacterial pathogenicity: Therapeutic implications

Abstract

Identification of the molecular mechanisms of host-pathogen interaction is becoming a key focus of proteomics. Analysis of these interactions holds promise for significant developments in the identification of new therapeutic strategies to combat infectious diseases, a process that will also benefit parallel improvements in molecular diagnostics, biomarker identification and drug discovery. This review highlights recent advances in functional proteomics initiatives in infectious disease with emphasis on studies undertaken within physiologically relevant parameters that enable identification of the infectious proteome rather than that of the vegetative state. Deciphering the molecular details of what constitutes physiologically relevant host-pathogen interactions remains an underdeveloped aspect of research into infectious disease. The magnitude of this deficit will be largely influenced by the ease with which model systems can be established to investigate such interactions. As the selective pressures exerted by the host on an infecting pathogen are numerous, the adequacy of certain model systems should be considered carefully.

Surface Proteome of “Mycobacterium avium subsp. hominissuis” during the Early Stages of Macrophage Infection

“…2, if the scope of reference is expanded to include proteins identified in published studies that comprehensively profile membrane, cell wall, and secreted proteins of M. marinum, M. avium subsp. paratuberculosis, and M. tuberculosis, the results indicate that ϳ90% of the proteins detected in this study are close homologues of proteins previously identified as plasma membrane, secreted, and/or cell wall-associated mycobacterial proteins (30,32,51,54,84,87) (see Table S1 in the supplemental material).…”

“…While previous studies have identified many of the cell membrane, cell wall, and surface-exposed proteins of related mycobacteria (30,32,51,54,74,84,87), little is known specifically about the surface-exposed proteome of M. avium subsp. hominissuis.…”

“…In most bacteria, elongation factor Tu serves a proof-reading function during ribosomal protein synthesis, a process which normally takes place in the cytoplasmic compartment (75). However, both elongation factor Tu and a range of ribosomal proteins have been consistently identified in studies of surface-exposed proteins in mycobacteria and related Gram-positive bacteria (1,5,32,74,80,87).…”

“…These proteins are also the primary target of the host immune system. Effective cellular and humoral immune responses depend on targeting accessible molecules, which tend to be on the surface of a pathogen (87). With respect to mycobacteria, putative and known surface-exposed proteins comprise a substantial proportion of antigens observed in comprehensive screens using sera from mycobacterium-infected hosts (37,42,45,85).…”

“…With respect to mycobacteria, putative and known surface-exposed proteins comprise a substantial proportion of antigens observed in comprehensive screens using sera from mycobacterium-infected hosts (37,42,45,85). The characterization of these proteins improves our understanding of bacterial pathogenesis and host immunity, providing insights that can lead to new diagnostic tools and vaccines (38,87).…”