Chemical Proteomics of Host–Microbe Interactions

Abstract

The dynamic proteome plays numerous roles in the interactions of microbes-whether they are invading pathogens or symbiotic organisms-and their hosts. Host and microbe sense, respond, and manipulate each other's biology via a multitude of mechanisms, resulting in alterations in protein expression or posttranslational modification that influence protein localization, activity, or binding partners. The intrinsic, temporal, and spatial complexity of multispecies systems makes identifying the molecular players challenging. Chemical proteomic approaches apply small molecule chemical tools to interrogate protein function, interactions or modifications. This review highlights recent advances in the application of these methods at the host-microbe interface.

Current Status of Proteomic Technologies for Discovering and Identifying Gingival Crevicular Fluid Biomarkers for Periodontal Disease

“…Proteins can be labeled metabolically with heavy or light isotope-containing growth media, and derivatization can occur following proteolytic digestion using isotopically distinct chemical labels or isobaric tags [57,58,59,60,61,62]. Other “label free” quantitation techniques eliminate labeling and instead rely on advanced software analyzes.…”

Metabolic labeling probes for interrogation of the host–pathogen interaction

“…A final area which is providing tantalizing new insights into the intracellular biology of the host-pathogen interaction is the use of probes to visualize the activity of specific pathogenic enzymes inside the host, so-called activity-based protein profiling (ABPP). 134 This approach has been used to image host cell alterations upon bacterial infection, 135,136 but the imaging of pathogenic enzymesparticularly those involved in virulence is an exciting new area. 134 An early example involved the use of the broad spectrum serine hydrolase probe FP-TAMRA ( Fig.…”

“…134 This approach has been used to image host cell alterations upon bacterial infection, 135,136 but the imaging of pathogenic enzymesparticularly those involved in virulence is an exciting new area. 134 An early example involved the use of the broad spectrum serine hydrolase probe FP-TAMRA ( Fig. 5) to identify the secreted serine hydrolases of Mtb 137,138 and V. cholera.…”

Activity-based protein profiling in bacteria: Applications for identification of therapeutic targets and characterization of microbial communities

“…Furthermore, it selects for enzymes that are amenable to modulation by small molecules and provides a platform to screen for selective inhibitors, even for enzymes with unknown function and unknown substrates, through competitive ABPP (Figure 1c) [7,12]. There are a number of excellent reviews that cover the application of ABPP to bacterial pathogenesis [13,14], host-microbe interactions [15,16], and host-associated and environmental microbial communities [17]. In addition, there have been many studies using affinity-based protein profiling (reviewed in [18]), which utilizes a photoreactive group to covalently label a target with the probe rather than relying on the reactivity of the catalytic residues of a target.…”