Keeping in Touch with Type-III Secretion System Effectors: Mass Spectrometry-Based Proteomics to Study Effector–Host Protein–Protein Interactions

Meyer, Margaux De; Ryck, Joren De; Goormachtig, Sofie; Damme, Petra Van

doi:10.3390/ijms21186891

Cited by 4 publications

(4 citation statements)

References 133 publications

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“…The future use of non-perturbing multimodal tags could be explored for studying bacterial effector biology as combining translocation dynamics together with purification or interactomics approaches could provide novel insights on an effector's function. For instance, the additional inclusion of a BioID tag (e.g., BirA*) for conducting proximity-dependent biotin labeling to enable the capture of interacting proteins-might allow the study of effector-host protein-protein interactions at selected timepoints during infection [109].…”

Section: Discussionmentioning

confidence: 99%

Recent Advancements in Tracking Bacterial Effector Protein Translocation

2022

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Bacteria-host interactions are characterized by the delivery of bacterial virulence factors, i.e., effectors, into host cells where they counteract host immunity and exploit host responses allowing bacterial survival and spreading. These effectors are translocated into host cells by means of dedicated secretion systems such as the type 3 secretion system (T3SS). A comprehensive understanding of effector translocation in a spatio-temporal manner is of critical importance to gain insights into an effector’s mode of action. Various approaches have been developed to understand timing and order of effector translocation, quantities of translocated effectors and their subcellular localization upon translocation into host cells. Recently, the existing toolset has been expanded by newly developed state-of-the art methods to monitor bacterial effector translocation and dynamics. In this review, we elaborate on reported methods and discuss recent advances and shortcomings in this area of tracking bacterial effector translocation.

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Section: Discussionmentioning

confidence: 99%

Recent Advancements in Tracking Bacterial Effector Protein Translocation

2022

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“…While BioID is limited to identifying targets presenting an accessible and free Lys residue to the bait, certain Gag-bait fusions may be hindered in VLP formation in Virotrap. Both state-of-the-art interactomics platforms represent a complementary means and may well-provide, depending on its specific biology, an extensive interactome for an effector protein of interest (44). Notably, a bias toward identifying SPI-2 effector targets during infection conditions-attributed to their timing of secretion and abundancy during infection-became apparent in the study by Walch and coworkers, and evident from the selection of five SPI-2 effectors for BioID interaction screening during infection (18,19).…”

Section: Discussionmentioning

confidence: 99%

Capturing Salmonella SspH2 Host Targets in Virus-Like Particles

et al. 2021

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In the context of host-pathogen interactions, gram-negative bacterial virulence factors, such as effectors, may be transferred from bacterial to eukaryotic host cytoplasm by multicomponent Type III protein secretion systems (T3SSs). Central to Salmonella enterica serovar Typhimurium (S. Typhimurium) pathogenesis is the secretion of over 40 effectors by two T3SSs encoded within pathogenicity islands SPI-1 and SPI-2. These effectors manipulate miscellaneous host cellular processes, such as cytoskeleton organization and immune signaling pathways, thereby permitting host colonization and bacterial dissemination. Recent research on effector biology provided mechanistic insights for some effectors. However, for many effectors, clearly defined roles and host target repertoires—further clarifying effector interconnectivity and virulence networks—are yet to be uncovered. Here we demonstrate the utility of the recently described viral-like particle trapping technology Virotrap as an effective approach to catalog S. Typhimurium effector-host protein complexes (EH-PCs). Mass spectrometry-based Virotrap analysis of the novel E3 ubiquitin ligase SspH2 previously shown to be implicated in modulating actin dynamics and immune signaling, exposed known host interactors PFN1 and−2 besides several putative novel, interconnected host targets. Network analysis revealed an actin (-binding) cluster among the significantly enriched hits for SspH2, consistent with the known localization of the S-palmitoylated effector with actin cytoskeleton components in the host. We show that Virotrap complements the current state-of-the-art toolkit to study protein complexes and represents a valuable means to screen for effector host targets in a high-throughput manner, thereby bridging the knowledge gap between effector-host interplay and pathogenesis.

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“…As many T3Es exert their function by binding with host proteins or metabolites, knowledge on their interactions is thus of fundamental importance. In this section, we will focus on different methods that can be used to elucidate effector-host protein–protein interactions (EH-PPI), each with their advantages and disadvantages as recently extensively reviewed ( Struk et al, 2019 ; De Meyer et al, 2020 ).…”

Section: Different Forensic Disciplines For the Functional Identifica...mentioning

confidence: 99%

From prediction to function: Current practices and challenges towards the functional characterization of type III effectors

2023

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The type III secretion system (T3SS) is a well-studied pathogenicity determinant of many bacteria through which effectors (T3Es) are translocated into the host cell, where they exercise a wide range of functions to deceive the host cell’s immunity and to establish a niche. Here we look at the different approaches that are used to functionally characterize a T3E. Such approaches include host localization studies, virulence screenings, biochemical activity assays, and large-scale omics, such as transcriptomics, interactomics, and metabolomics, among others. By means of the phytopathogenic Ralstonia solanacearum species complex (RSSC) as a case study, the current advances of these methods will be explored, alongside the progress made in understanding effector biology. Data obtained by such complementary methods provide crucial information to comprehend the entire function of the effectome and will eventually lead to a better understanding of the phytopathogen, opening opportunities to tackle it.

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Keeping in Touch with Type-III Secretion System Effectors: Mass Spectrometry-Based Proteomics to Study Effector–Host Protein–Protein Interactions

Cited by 4 publications

References 133 publications

Recent Advancements in Tracking Bacterial Effector Protein Translocation

Recent Advancements in Tracking Bacterial Effector Protein Translocation

Capturing Salmonella SspH2 Host Targets in Virus-Like Particles

From prediction to function: Current practices and challenges towards the functional characterization of type III effectors

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