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Capturing Salmonella SspH2 Host Targets in Virus-Like Particles
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)...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455821/ https://www.ncbi.nlm.nih.gov/pubmed/34568381 http://dx.doi.org/10.3389/fmed.2021.725072 |
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author | De Meyer, Margaux Fijalkowski, Igor Jonckheere, Veronique De Sutter, Delphine Eyckerman, Sven Van Damme, Petra |
author_facet | De Meyer, Margaux Fijalkowski, Igor Jonckheere, Veronique De Sutter, Delphine Eyckerman, Sven Van Damme, Petra |
author_sort | De Meyer, Margaux |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8455821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84558212021-09-23 Capturing Salmonella SspH2 Host Targets in Virus-Like Particles De Meyer, Margaux Fijalkowski, Igor Jonckheere, Veronique De Sutter, Delphine Eyckerman, Sven Van Damme, Petra Front Med (Lausanne) Medicine 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. Frontiers Media S.A. 2021-09-08 /pmc/articles/PMC8455821/ /pubmed/34568381 http://dx.doi.org/10.3389/fmed.2021.725072 Text en Copyright © 2021 De Meyer, Fijalkowski, Jonckheere, De Sutter, Eyckerman and Van Damme. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine De Meyer, Margaux Fijalkowski, Igor Jonckheere, Veronique De Sutter, Delphine Eyckerman, Sven Van Damme, Petra Capturing Salmonella SspH2 Host Targets in Virus-Like Particles |
title | Capturing Salmonella SspH2 Host Targets in Virus-Like Particles |
title_full | Capturing Salmonella SspH2 Host Targets in Virus-Like Particles |
title_fullStr | Capturing Salmonella SspH2 Host Targets in Virus-Like Particles |
title_full_unstemmed | Capturing Salmonella SspH2 Host Targets in Virus-Like Particles |
title_short | Capturing Salmonella SspH2 Host Targets in Virus-Like Particles |
title_sort | capturing salmonella ssph2 host targets in virus-like particles |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455821/ https://www.ncbi.nlm.nih.gov/pubmed/34568381 http://dx.doi.org/10.3389/fmed.2021.725072 |
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