Contributions of Mass Spectrometry-Based Proteomics to Understanding Salmonella-Host Interactions

Abstract

As a model pathogen, Salmonella invades both phagocytic and non-phagocytic host cells and adopts an intracellular lifestyle in a membrane-bound compartment during infection. Therefore, a systemic overview of Salmonella adaptations to distinct host cells together with host remodeling will assist us in charting the landscape of host-pathogen interactions. Central to the Salmonella-host interplay are bacterial virulence factors (effectors) that are injected into host cells by type III secretion systems (T3SSs). Despite great progress, functional studies of bacterial effectors have experienced daunting challenges as well. In the last decade, mass spectrometry-based proteomics has evolved into a powerful technological platform that can quantitatively measure thousands of proteins in terms of their expression as well as post-translational modifications. Here, we will review the applications of high-throughput proteomic technologies in understanding the dynamic reprogramming of both Salmonella and host proteomes during the course of infection. Furthermore, we will summarize the progress in utilizing affinity purification-mass spectrometry to screen for host substrates of Salmonella T3SS effectors. Finally, we will critically discuss some limitations/challenges with current proteomic platforms in the context of host-pathogen interactions and highlight some emerging technologies that may offer the promise of tackling these problems.

Deep proteome coverage advances knowledge of Treponema pallidum protein expression profiles during infection

“…); (2) examination and inter-strain comparison of specific protein expression profiles (e.g. proteins pertaining to virulence [virulence factors]); (3) confirmation and inter-strain comparison of the expression of functionally-unannotated proteins and “hypothetical proteins” that may play important roles in microbial biology and pathogenesis 21 , 22 ; and (4) the identification of proteins that are essential for basic functioning and survival. The T. pallidum genome contains approximately 1000 predicted protein-coding genes 15 .…”

Proteomic Approaches to Unravel Mechanisms of Antibiotic Resistance and Immune Evasion of Bacterial Pathogens

“…These host–pathogen interactions are highly dynamic across all stages of pathogenic infection, and the immune system’s response to pathogen-associated molecular pattern (PAMP) activation of immediate host inflammatory and antimicrobial responses ( 89 ). Direct measurement of dynamic protein abundance (i.e., expression profiling) from both bacteria and host cells in infection models, therefore, offers unique holistic insights into those molecular mechanisms underlying bacterial pathogenesis ( 90 , 91 ). In this regard, studies of proteomic profiling of bacteria and other intracellular pathogens recovered from infected host cells, seems to lead that of studies examining the mammalian host, partly due to the relatively compact size of bacterial proteomes.…”

Determination of the Salmonella intracellular lifestyle by the diversified interaction of Type III secretion system effectors and host GTPases

“…MS‐based proteomics has become a powerful tool for systematically studying the interplay between host proteins and bacterial virulence factors (Y. Yang et al, 2015). Recent proteomics studies show a complicated regulatory network between GTPase proteins and T3SS effectors in shaping the intracellular lifestyle of Salmonella (Liu et al, 2015; Vogels et al, 2011; B. Zhang et al, 2020). The interaction of T3SS effectors‐GTPases may also control the Salmonella adaptions to different cell types.…”

“…Yang et al, 2015). Recent proteomics studies show a complicated regulatory network between GTPase proteins and T3SS effectors in shaping the intracellular lifestyle of Salmonella (Liu et al, 2015;Vogels et al, 2011;B. Zhang et al, 2020).…”