O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE
For successful colonization, pathogenic bacteria need to adapt their metabolism and virulence functions to challenging environments within their mammalian hosts that are frequently characterized by low oxygen (O2) tensions. Upon oral ingestion, the human pathogen Salmonella enterica serovar Typhimur...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1434254/full |
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| author | Steffi Walter Valentin Schatz Valentin Schatz Valentin Schatz Jana Petzold Christiane Schmidt Stefanie Hoffmann Jonathan Jantsch Jonathan Jantsch Jonathan Jantsch Roman G. Gerlach Roman G. Gerlach |
| author_facet | Steffi Walter Valentin Schatz Valentin Schatz Valentin Schatz Jana Petzold Christiane Schmidt Stefanie Hoffmann Jonathan Jantsch Jonathan Jantsch Jonathan Jantsch Roman G. Gerlach Roman G. Gerlach |
| author_sort | Steffi Walter |
| collection | DOAJ |
| description | For successful colonization, pathogenic bacteria need to adapt their metabolism and virulence functions to challenging environments within their mammalian hosts that are frequently characterized by low oxygen (O2) tensions. Upon oral ingestion, the human pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) is exposed to changing O2 and pH levels. Low concentrations of O2, which can enhance the virulence of enteroinvasive pathogens, facilitate the expression of the type three secretion system (T3SS-1) encoded by the Salmonella pathogenicity island 1 (SPI-1) that is critical for enteroinvasion and pathogenicity of S. Typhimurium. To study the impact of key environmental cues of the intestine when Salmonella encounter enterocytes, we established an in vitro growth model, which allows shifting the concentration of O2 from 0.5% to 11% and the pH from 5.9 to 7.4 in the presence of acetate and the alternative electron acceptor nitrate. Compared to normoxia, hypoxia elevated the expression of SPI-1 genes encoding T3SS-1 translocators and effectors, which resulted in higher invasion and effector translocation in epithelial cells. While hypoxia and pH shift only marginally altered the gene expression of SPI-1 regulators, including the SPI-1 repressor hilE, hypoxia and pH shift completely incapacitated HilE in a post-translational manner, ultimately promoting SPI-1 activity. From these findings, we conclude that O2-dependent HilE function allows for ultrasensitive adaptation of SPI-1 activity in environments with varying O2 availability such as the intestinal tract. |
| format | Article |
| id | doaj-art-7f4c271c950040baa6325cecace26321 |
| institution | DOAJ |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-7f4c271c950040baa6325cecace263212025-08-20T03:01:03ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-02-011510.3389/fcimb.2025.14342541434254O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilESteffi Walter0Valentin Schatz1Valentin Schatz2Valentin Schatz3Jana Petzold4Christiane Schmidt5Stefanie Hoffmann6Jonathan Jantsch7Jonathan Jantsch8Jonathan Jantsch9Roman G. Gerlach10Roman G. Gerlach11Project Group 5, Robert Koch Institute, Wernigerode, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg and University of Regensburg, Regensburg, GermanyInstitute for Medical Microbiology, Immunology, and Hygiene, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyMikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, GermanyProject Group 5, Robert Koch Institute, Wernigerode, GermanyProject Group 5, Robert Koch Institute, Wernigerode, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg and University of Regensburg, Regensburg, GermanyInstitute for Medical Microbiology, Immunology, and Hygiene, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyProject Group 5, Robert Koch Institute, Wernigerode, GermanyMikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, GermanyFor successful colonization, pathogenic bacteria need to adapt their metabolism and virulence functions to challenging environments within their mammalian hosts that are frequently characterized by low oxygen (O2) tensions. Upon oral ingestion, the human pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) is exposed to changing O2 and pH levels. Low concentrations of O2, which can enhance the virulence of enteroinvasive pathogens, facilitate the expression of the type three secretion system (T3SS-1) encoded by the Salmonella pathogenicity island 1 (SPI-1) that is critical for enteroinvasion and pathogenicity of S. Typhimurium. To study the impact of key environmental cues of the intestine when Salmonella encounter enterocytes, we established an in vitro growth model, which allows shifting the concentration of O2 from 0.5% to 11% and the pH from 5.9 to 7.4 in the presence of acetate and the alternative electron acceptor nitrate. Compared to normoxia, hypoxia elevated the expression of SPI-1 genes encoding T3SS-1 translocators and effectors, which resulted in higher invasion and effector translocation in epithelial cells. While hypoxia and pH shift only marginally altered the gene expression of SPI-1 regulators, including the SPI-1 repressor hilE, hypoxia and pH shift completely incapacitated HilE in a post-translational manner, ultimately promoting SPI-1 activity. From these findings, we conclude that O2-dependent HilE function allows for ultrasensitive adaptation of SPI-1 activity in environments with varying O2 availability such as the intestinal tract.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1434254/fullSalmonellatype three secretionhypoxiaSalmonella pathogenicity islandin vitro model |
| spellingShingle | Steffi Walter Valentin Schatz Valentin Schatz Valentin Schatz Jana Petzold Christiane Schmidt Stefanie Hoffmann Jonathan Jantsch Jonathan Jantsch Jonathan Jantsch Roman G. Gerlach Roman G. Gerlach O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE Frontiers in Cellular and Infection Microbiology Salmonella type three secretion hypoxia Salmonella pathogenicity island in vitro model |
| title | O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE |
| title_full | O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE |
| title_fullStr | O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE |
| title_full_unstemmed | O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE |
| title_short | O2-dependent incapacitation of the Salmonella pathogenicity island 1 repressor HilE |
| title_sort | o2 dependent incapacitation of the salmonella pathogenicity island 1 repressor hile |
| topic | Salmonella type three secretion hypoxia Salmonella pathogenicity island in vitro model |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1434254/full |
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