Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC
ABSTRACT Bacterial flagellin activates the host immune system and triggers pyroptosis. Salmonella reduces flagellin expression when it survives within host cells. Here, we found that the UMPylator YdiU significantly altered the Salmonella flagellar biogenesis process upon host cell entry. The expres...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-06-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00249-22 |
| _version_ | 1811342715107934208 |
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| author | Yue Ma Yingying Yue Haihong Jia Nannan Song Li Zhai Weiwei Wang Cuiling Li Bingqing Li |
| author_facet | Yue Ma Yingying Yue Haihong Jia Nannan Song Li Zhai Weiwei Wang Cuiling Li Bingqing Li |
| author_sort | Yue Ma |
| collection | DOAJ |
| description | ABSTRACT Bacterial flagellin activates the host immune system and triggers pyroptosis. Salmonella reduces flagellin expression when it survives within host cells. Here, we found that the UMPylator YdiU significantly altered the Salmonella flagellar biogenesis process upon host cell entry. The expression levels of class II and class III flagellar genes, but not the class I flagellar genes flhDC, were dramatically increased in a ΔydiU strain compared to wild-type (WT) Salmonella in a host-simulating environment. A direct interaction between YdiU and FlhDC was detected by bacterial two-hybrid assay. Furthermore, YdiU efficiently catalyzed the UMPylation of FlhC but not FlhD, FliA, or FliC. UMPylation of FlhC completely eliminated its DNA-binding activity. In vivo experiments showed that YdiU was required and sufficient for Salmonella flagellar control within host cells. Mice infected with the ΔydiU strain died much earlier than WT strain-infected mice and developed much more severe inflammation and injury in organs and much higher levels of cytokines in blood, demonstrating that early host death induced by the ΔydiU strain is probably due to excessive inflammation. Our results indicate that YdiU acts as an essential factor of Salmonella to mediate host immune escape. IMPORTANCE Salmonella is an important facultative pathogen of foodborne illness and typhoid fever in humans. Flagella allow bacterial motility and are required for Salmonella to successfully invade the host cells. In parallel, flagellin triggers the host immune system. Salmonella reduces flagellar biogenesis to avoid detection within host cells by a largely unknown mechanism. Here, we report that the UMPylator YdiU inhibits flagellin expression in response to host signals in an UMPylation-dependent manner. The target of YdiU is the major flagellar transcription factor FlhDC. YdiU UMPylates the FlhC subunit on its Ser31 residue and prevents FlhDC from binding to flagellar genes, thus switching off flagellar biogenesis. Our results reveal a novel mechanism by which Salmonella adopts posttranslational modification to shut down flagellar synthesis as a strategy to achieve immune escape. |
| first_indexed | 2024-04-13T19:16:54Z |
| format | Article |
| id | doaj.art-7f7e0b755d034555860d1185977359a1 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-13T19:16:54Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-7f7e0b755d034555860d1185977359a12022-12-22T02:33:40ZengAmerican Society for MicrobiologymBio2150-75112022-06-0113310.1128/mbio.00249-22Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDCYue Ma0Yingying Yue1Haihong Jia2Nannan Song3Li Zhai4Weiwei Wang5Cuiling Li6Bingqing Li7Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Pathogen Biology, School of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaABSTRACT Bacterial flagellin activates the host immune system and triggers pyroptosis. Salmonella reduces flagellin expression when it survives within host cells. Here, we found that the UMPylator YdiU significantly altered the Salmonella flagellar biogenesis process upon host cell entry. The expression levels of class II and class III flagellar genes, but not the class I flagellar genes flhDC, were dramatically increased in a ΔydiU strain compared to wild-type (WT) Salmonella in a host-simulating environment. A direct interaction between YdiU and FlhDC was detected by bacterial two-hybrid assay. Furthermore, YdiU efficiently catalyzed the UMPylation of FlhC but not FlhD, FliA, or FliC. UMPylation of FlhC completely eliminated its DNA-binding activity. In vivo experiments showed that YdiU was required and sufficient for Salmonella flagellar control within host cells. Mice infected with the ΔydiU strain died much earlier than WT strain-infected mice and developed much more severe inflammation and injury in organs and much higher levels of cytokines in blood, demonstrating that early host death induced by the ΔydiU strain is probably due to excessive inflammation. Our results indicate that YdiU acts as an essential factor of Salmonella to mediate host immune escape. IMPORTANCE Salmonella is an important facultative pathogen of foodborne illness and typhoid fever in humans. Flagella allow bacterial motility and are required for Salmonella to successfully invade the host cells. In parallel, flagellin triggers the host immune system. Salmonella reduces flagellar biogenesis to avoid detection within host cells by a largely unknown mechanism. Here, we report that the UMPylator YdiU inhibits flagellin expression in response to host signals in an UMPylation-dependent manner. The target of YdiU is the major flagellar transcription factor FlhDC. YdiU UMPylates the FlhC subunit on its Ser31 residue and prevents FlhDC from binding to flagellar genes, thus switching off flagellar biogenesis. Our results reveal a novel mechanism by which Salmonella adopts posttranslational modification to shut down flagellar synthesis as a strategy to achieve immune escape.https://journals.asm.org/doi/10.1128/mbio.00249-22FlhDCSalmonellaUMPylationYdiUflagellar gene regulation |
| spellingShingle | Yue Ma Yingying Yue Haihong Jia Nannan Song Li Zhai Weiwei Wang Cuiling Li Bingqing Li Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC mBio FlhDC Salmonella UMPylation YdiU flagellar gene regulation |
| title | Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC |
| title_full | Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC |
| title_fullStr | Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC |
| title_full_unstemmed | Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC |
| title_short | Switching off Bacterial Flagellar Biogenesis by YdiU-Mediated UMPylation of FlhDC |
| title_sort | switching off bacterial flagellar biogenesis by ydiu mediated umpylation of flhdc |
| topic | FlhDC Salmonella UMPylation YdiU flagellar gene regulation |
| url | https://journals.asm.org/doi/10.1128/mbio.00249-22 |
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