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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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Autores principales: Chen, Fei, Cui, Guolin, Wang, Shuxia, Nair, Manoj Kumar Mohan, He, Lihong, Qi, Xinyi, Han, Xiangmin, Zhang, Hanqi, Zhang, Jing-Ren, Su, Jingliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567169/
https://www.ncbi.nlm.nih.gov/pubmed/28745311
http://dx.doi.org/10.1038/emi.2017.53
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author Chen, Fei
Cui, Guolin
Wang, Shuxia
Nair, Manoj Kumar Mohan
He, Lihong
Qi, Xinyi
Han, Xiangmin
Zhang, Hanqi
Zhang, Jing-Ren
Su, Jingliang
author_facet Chen, Fei
Cui, Guolin
Wang, Shuxia
Nair, Manoj Kumar Mohan
He, Lihong
Qi, Xinyi
Han, Xiangmin
Zhang, Hanqi
Zhang, Jing-Ren
Su, Jingliang
author_sort Chen, Fei
collection PubMed
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.
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spelling pubmed-55671692017-08-30 Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS Chen, Fei Cui, Guolin Wang, Shuxia Nair, Manoj Kumar Mohan He, Lihong Qi, Xinyi Han, Xiangmin Zhang, Hanqi Zhang, Jing-Ren Su, Jingliang Emerg Microbes Infect Original Article 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. Nature Publishing Group 2017-07 2017-07-26 /pmc/articles/PMC5567169/ /pubmed/28745311 http://dx.doi.org/10.1038/emi.2017.53 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Chen, Fei
Cui, Guolin
Wang, Shuxia
Nair, Manoj Kumar Mohan
He, Lihong
Qi, Xinyi
Han, Xiangmin
Zhang, Hanqi
Zhang, Jing-Ren
Su, Jingliang
Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS
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 Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567169/
https://www.ncbi.nlm.nih.gov/pubmed/28745311
http://dx.doi.org/10.1038/emi.2017.53
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