EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals.
Attaching/Effacing (A/E) bacteria include human pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and their murine equivalent Citrobacter rodentium (CR), of which EPEC and EHEC are important causative agents of foodborne diseases worldwide. While A/E pathogen infe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007898 |
| _version_ | 1819007572777107456 |
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| author | Xue Xia Yue Liu Andrea Hodgson Dongqing Xu Wenxuan Guo Hongbing Yu Weifeng She Chenxing Zhou Lei Lan Kai Fu Bruce A Vallance Fengyi Wan |
| author_facet | Xue Xia Yue Liu Andrea Hodgson Dongqing Xu Wenxuan Guo Hongbing Yu Weifeng She Chenxing Zhou Lei Lan Kai Fu Bruce A Vallance Fengyi Wan |
| author_sort | Xue Xia |
| collection | DOAJ |
| description | Attaching/Effacing (A/E) bacteria include human pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and their murine equivalent Citrobacter rodentium (CR), of which EPEC and EHEC are important causative agents of foodborne diseases worldwide. While A/E pathogen infections cause mild symptoms in the immunocompetent hosts, an increasing number of studies show that they produce more severe morbidity and mortality in immunocompromised and/or immunodeficient hosts. However, the pathogenic mechanisms and crucial host-pathogen interactions during A/E pathogen infections under immunocompromised conditions remain elusive. We performed a functional screening by infecting interleukin-22 (IL-22) knockout (Il22-/-) mice with a library of randomly mutated CR strains. Our screen reveals that interruption of the espF gene, which encodes the Type III Secretion System effector EspF (E. coli secreted protein F) conserved among A/E pathogens, completely abolishes the high mortality rates in CR-infected Il22-/- mice. Chromosomal deletion of espF in CR recapitulates the avirulent phenotype without impacting colonization and proliferation of CR, and EspF complement in ΔespF strain fully restores the virulence in mice. Moreover, the expression levels of the espF gene are elevated during CR infection and CR induces disruption of the tight junction (TJ) strands in colonic epithelium in an EspF-dependent manner. Distinct from EspF, chromosomal deletion of other known TJ-damaging effector genes espG and map failed to impede CR virulence in Il22-/- mice. Hence our findings unveil a critical pathophysiological function for EspF during CR infection in the immunocompromised host and provide new insights into the complex pathogenic mechanisms of A/E pathogens. |
| first_indexed | 2024-12-21T00:26:43Z |
| format | Article |
| id | doaj.art-3998c08814ba41c4afc823c4cc8e2e8f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T00:26:43Z |
| publishDate | 2019-06-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Pathogens |
| spelling | doaj.art-3998c08814ba41c4afc823c4cc8e2e8f2022-12-21T19:21:58ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-06-01156e100789810.1371/journal.ppat.1007898EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals.Xue XiaYue LiuAndrea HodgsonDongqing XuWenxuan GuoHongbing YuWeifeng SheChenxing ZhouLei LanKai FuBruce A VallanceFengyi WanAttaching/Effacing (A/E) bacteria include human pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and their murine equivalent Citrobacter rodentium (CR), of which EPEC and EHEC are important causative agents of foodborne diseases worldwide. While A/E pathogen infections cause mild symptoms in the immunocompetent hosts, an increasing number of studies show that they produce more severe morbidity and mortality in immunocompromised and/or immunodeficient hosts. However, the pathogenic mechanisms and crucial host-pathogen interactions during A/E pathogen infections under immunocompromised conditions remain elusive. We performed a functional screening by infecting interleukin-22 (IL-22) knockout (Il22-/-) mice with a library of randomly mutated CR strains. Our screen reveals that interruption of the espF gene, which encodes the Type III Secretion System effector EspF (E. coli secreted protein F) conserved among A/E pathogens, completely abolishes the high mortality rates in CR-infected Il22-/- mice. Chromosomal deletion of espF in CR recapitulates the avirulent phenotype without impacting colonization and proliferation of CR, and EspF complement in ΔespF strain fully restores the virulence in mice. Moreover, the expression levels of the espF gene are elevated during CR infection and CR induces disruption of the tight junction (TJ) strands in colonic epithelium in an EspF-dependent manner. Distinct from EspF, chromosomal deletion of other known TJ-damaging effector genes espG and map failed to impede CR virulence in Il22-/- mice. Hence our findings unveil a critical pathophysiological function for EspF during CR infection in the immunocompromised host and provide new insights into the complex pathogenic mechanisms of A/E pathogens.https://doi.org/10.1371/journal.ppat.1007898 |
| spellingShingle | Xue Xia Yue Liu Andrea Hodgson Dongqing Xu Wenxuan Guo Hongbing Yu Weifeng She Chenxing Zhou Lei Lan Kai Fu Bruce A Vallance Fengyi Wan EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals. PLoS Pathogens |
| title | EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals. |
| title_full | EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals. |
| title_fullStr | EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals. |
| title_full_unstemmed | EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals. |
| title_short | EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals. |
| title_sort | espf is crucial for citrobacter rodentium induced tight junction disruption and lethality in immunocompromised animals |
| url | https://doi.org/10.1371/journal.ppat.1007898 |
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