Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS
Francisella tularensis is a highly infectious intracellular pathogen that infects a wide range of host species and causes fatal pneumonic tularemia in humans. ftlA was identified as a potential virulence determinant of the F. tularensis live vaccine strain (LVS) in our previous transposon screen, bu...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1038/emi.2017.53 |
| _version_ | 1797676908127715328 |
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| author | Fei Chen Guolin Cui Shuxia Wang Manoj Kumar Mohan Nair Lihong He Xinyi Qi Xiangmin Han Hanqi Zhang Jing-Ren Zhang Jingliang Su |
| author_facet | Fei Chen Guolin Cui Shuxia Wang Manoj Kumar Mohan Nair Lihong He Xinyi Qi Xiangmin Han Hanqi Zhang Jing-Ren Zhang Jingliang Su |
| author_sort | Fei Chen |
| collection | DOAJ |
| description | Francisella tularensis is a highly infectious intracellular pathogen that infects a wide range of host species and causes fatal pneumonic tularemia in humans. ftlA was identified as a potential virulence determinant of the F. tularensis live vaccine strain (LVS) in our previous transposon screen, but its function remained undefined. Here, we show that an unmarked deletion mutant of ftlA was avirulent in a pneumonia mouse model with a severely impaired capacity to infect host cells. Consistent with its sequence homology with GDSL lipase/esterase family proteins, the FtlA protein displayed lipolytic activity in both E. coli and F. tularensis with a preference for relatively short carbon-chain substrates. FtlA thus represents the first F. tularensis lipase to promote bacterial infection of host cells and in vivo fitness. As a cytoplasmic protein, we found that FtlA was secreted into the extracellular environment as a component of outer membrane vesicles (OMVs). Further confocal microscopy analysis revealed that the FtlA-containing OMVs isolated from F. tularensis LVS attached to the host cell membrane. Finally, the OMV-associated FtlA protein complemented the genetic deficiency of the ΔftlA mutant in terms of host cell infection when OMVs purified from the parent strain were co-incubated with the mutant bacteria. These lines of evidence strongly suggest that the FtlA lipase promotes F. tularensis adhesion and internalization by modifying bacterial and/or host molecule(s) when it is secreted as a component of OMVs.Emerging Microbes & Infections (2017) 6, e66; doi:10.1038/emi.2017.53; published online 26 July 2017 |
| first_indexed | 2024-03-11T22:37:16Z |
| format | Article |
| id | doaj.art-cf053df9fd784555b1a3bf34b806eff8 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-11T22:37:16Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-cf053df9fd784555b1a3bf34b806eff82023-09-22T12:08:35ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512017-01-016111210.1038/emi.2017.53Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVSFei Chen0Guolin Cui1Shuxia Wang2Manoj Kumar Mohan Nair3Lihong He4Xinyi Qi5Xiangmin Han6Hanqi Zhang7Jing-Ren Zhang8Jingliang Su9Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaBeckman Coulter, 36 Cherry Hill Drive, Danvers, MA 01923, USACenter for Infectious Disease Research, School of MedicineTsinghua University, Beijing 100084, ChinaKey Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaKey Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaCenter for Infectious Disease Research, School of MedicineTsinghua University, Beijing 100084, ChinaKey Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary MedicineChina Agricultural University, Beijing 100193, ChinaFrancisella tularensis is a highly infectious intracellular pathogen that infects a wide range of host species and causes fatal pneumonic tularemia in humans. ftlA was identified as a potential virulence determinant of the F. tularensis live vaccine strain (LVS) in our previous transposon screen, but its function remained undefined. Here, we show that an unmarked deletion mutant of ftlA was avirulent in a pneumonia mouse model with a severely impaired capacity to infect host cells. Consistent with its sequence homology with GDSL lipase/esterase family proteins, the FtlA protein displayed lipolytic activity in both E. coli and F. tularensis with a preference for relatively short carbon-chain substrates. FtlA thus represents the first F. tularensis lipase to promote bacterial infection of host cells and in vivo fitness. As a cytoplasmic protein, we found that FtlA was secreted into the extracellular environment as a component of outer membrane vesicles (OMVs). Further confocal microscopy analysis revealed that the FtlA-containing OMVs isolated from F. tularensis LVS attached to the host cell membrane. Finally, the OMV-associated FtlA protein complemented the genetic deficiency of the ΔftlA mutant in terms of host cell infection when OMVs purified from the parent strain were co-incubated with the mutant bacteria. These lines of evidence strongly suggest that the FtlA lipase promotes F. tularensis adhesion and internalization by modifying bacterial and/or host molecule(s) when it is secreted as a component of OMVs.Emerging Microbes & Infections (2017) 6, e66; doi:10.1038/emi.2017.53; published online 26 July 2017https://www.tandfonline.com/doi/10.1038/emi.2017.53Francisella tularensisFTL_0430FtlAintracellular infectionlipaseouter membrane vesicle |
| spellingShingle | Fei Chen Guolin Cui Shuxia Wang Manoj Kumar Mohan Nair Lihong He Xinyi Qi Xiangmin Han Hanqi Zhang Jing-Ren Zhang Jingliang Su Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS Emerging Microbes and Infections Francisella tularensis FTL_0430 FtlA intracellular infection lipase outer membrane vesicle |
| title | Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS |
| title_full | Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS |
| title_fullStr | Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS |
| title_full_unstemmed | Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS |
| title_short | Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS |
| title_sort | outer membrane vesicle associated lipase ftla enhances cellular invasion and virulence in francisella tularensis lvs |
| topic | Francisella tularensis FTL_0430 FtlA intracellular infection lipase outer membrane vesicle |
| url | https://www.tandfonline.com/doi/10.1038/emi.2017.53 |
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