Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis
Mechanisms of host–pathogen interactions resulting in immunopathological responses upon human Campylobacter jejuni infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-11-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19490976.2020.1770017 |
| _version_ | 1818878646510682112 |
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| author | Markus M. Heimesaat Anna-Maria Schmidt Soraya Mousavi Ulrike Escher Nicole Tegtmeyer Silja Wessler Gabriele Gadermaier Peter Briza Dirk Hofreuter Stefan Bereswill Steffen Backert |
| author_facet | Markus M. Heimesaat Anna-Maria Schmidt Soraya Mousavi Ulrike Escher Nicole Tegtmeyer Silja Wessler Gabriele Gadermaier Peter Briza Dirk Hofreuter Stefan Bereswill Steffen Backert |
| author_sort | Markus M. Heimesaat |
| collection | DOAJ |
| description | Mechanisms of host–pathogen interactions resulting in immunopathological responses upon human Campylobacter jejuni infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen for proteases expressed by C. jejuni, we identified a peptidase of the M24 family as a potential novel virulence factor, which was named PepP. The gene is strongly conserved in various Campylobacter species. A constructed deletion mutant ΔpepP of C. jejuni strain 81–176 grew as efficiently compared to isogenic wild-type (WT) or pepP complemented bacteria. To shed light on the potential role of this protease in mediating immunopathological responses in the mammalian host, we perorally challenged microbiota-depleted IL-10−/- mice with these strains. All strains stably colonized the murine gastrointestinal tract with comparably high loads. Remarkably, pepP deficiency was associated with less severe induced malaise, with less distinct apoptotic and innate immune cell responses, but also with more pronounced proliferative/regenerative epithelial cell responses in the large intestine at d6post-infection. Furthermore, pro-inflammatory mediators were lower in the colon, ileum, and mesenteric lymph nodes of mice that had been challenged with the ΔpepP mutant compared to the WT or pepP complemented strains. This also held true for extra-intestinal organs including liver, kidneys, and lungs, and, strikingly, to systemic compartments. Taken together, protease PepP is a novel virulence determinant involved in mediating campylobacteriosis. The finding that apoptosis in the colon is significantly diminished in mice infected with the pepP mutant highlights the epithelial layer as the first and main target of PepP in the intestine. |
| first_indexed | 2024-12-19T14:17:29Z |
| format | Article |
| id | doaj.art-bf79937d2d4a4cef9a4a8b30dc2aef44 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-12-19T14:17:29Z |
| publishDate | 2020-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-bf79937d2d4a4cef9a4a8b30dc2aef442022-12-21T20:17:56ZengTaylor & Francis GroupGut Microbes1949-09761949-09842020-11-0112110.1080/19490976.2020.17700171770017Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosisMarkus M. Heimesaat0Anna-Maria Schmidt1Soraya Mousavi2Ulrike Escher3Nicole Tegtmeyer4Silja Wessler5Gabriele Gadermaier6Peter Briza7Dirk Hofreuter8Stefan Bereswill9Steffen Backert10And Berlin Institute of HealthAnd Berlin Institute of HealthAnd Berlin Institute of HealthAnd Berlin Institute of HealthFriedrich Alexander University Erlangen/NurembergParis Lodron University of SalzburgParis Lodron University of SalzburgParis Lodron University of SalzburgGerman Federal Institute for Risk Assessment (Bfr)And Berlin Institute of HealthFriedrich Alexander University Erlangen/NurembergMechanisms of host–pathogen interactions resulting in immunopathological responses upon human Campylobacter jejuni infection are not completely understood, but the recent availability of murine infection models mimicking key features of campylobacteriosis helps solving this dilemma. During a screen for proteases expressed by C. jejuni, we identified a peptidase of the M24 family as a potential novel virulence factor, which was named PepP. The gene is strongly conserved in various Campylobacter species. A constructed deletion mutant ΔpepP of C. jejuni strain 81–176 grew as efficiently compared to isogenic wild-type (WT) or pepP complemented bacteria. To shed light on the potential role of this protease in mediating immunopathological responses in the mammalian host, we perorally challenged microbiota-depleted IL-10−/- mice with these strains. All strains stably colonized the murine gastrointestinal tract with comparably high loads. Remarkably, pepP deficiency was associated with less severe induced malaise, with less distinct apoptotic and innate immune cell responses, but also with more pronounced proliferative/regenerative epithelial cell responses in the large intestine at d6post-infection. Furthermore, pro-inflammatory mediators were lower in the colon, ileum, and mesenteric lymph nodes of mice that had been challenged with the ΔpepP mutant compared to the WT or pepP complemented strains. This also held true for extra-intestinal organs including liver, kidneys, and lungs, and, strikingly, to systemic compartments. Taken together, protease PepP is a novel virulence determinant involved in mediating campylobacteriosis. The finding that apoptosis in the colon is significantly diminished in mice infected with the pepP mutant highlights the epithelial layer as the first and main target of PepP in the intestine.http://dx.doi.org/10.1080/19490976.2020.1770017campylobacteriosissecondary abiotic il-10−/- mouse modelpro-inflammatory immune responsesm24 peptidase familyxaa-pro aminopeptidasepepphost–pathogen interaction |
| spellingShingle | Markus M. Heimesaat Anna-Maria Schmidt Soraya Mousavi Ulrike Escher Nicole Tegtmeyer Silja Wessler Gabriele Gadermaier Peter Briza Dirk Hofreuter Stefan Bereswill Steffen Backert Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis Gut Microbes campylobacteriosis secondary abiotic il-10−/- mouse model pro-inflammatory immune responses m24 peptidase family xaa-pro aminopeptidase pepp host–pathogen interaction |
| title | Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis |
| title_full | Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis |
| title_fullStr | Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis |
| title_full_unstemmed | Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis |
| title_short | Peptidase PepP is a novel virulence factor of Campylobacter jejuni contributing to murine campylobacteriosis |
| title_sort | peptidase pepp is a novel virulence factor of campylobacter jejuni contributing to murine campylobacteriosis |
| topic | campylobacteriosis secondary abiotic il-10−/- mouse model pro-inflammatory immune responses m24 peptidase family xaa-pro aminopeptidase pepp host–pathogen interaction |
| url | http://dx.doi.org/10.1080/19490976.2020.1770017 |
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