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Type 1 secretion system in Legionella pneumophila : substrate localization and role during the infectious cycle

Abstract : Legionella pneumophila is the causative agent of a form of pneumonia called legionellosis or Legionnaires’ disease. Between 2012 and 2015, the reported European cases of legionellosis increased from 5,848 to 7,069 cases per year where France, Germany, Italy and Spain accounted for 69% of the reported cases. Worryingly, the case fatality of incidents was 8.2% making this disease a considerable health concern. One virulence factor produced by this bacterium is a large protein (~700 kDa) belonging to the RTX (Repeats in ToXin) family called RtxA secreted by the type 1 secretion system. The hereby work reveals that, in vitro, LapG periplasmic protease cleaves RtxA N-terminus in the middle of a di-alanine motif (a.a. 108-109). We also show using lapG and lapD mutant strains, that RtxA release is controlled by these two proteins similar to Pseudomonas fluorescenes LapA. We observed that a strain lacking LapG protease maintains RtxA on the cell surface, while a strain lacking LapD does not exhibit cell surface RtxA. Interestingly, we identified the presence of homologous potential T1SS/LapDG systems in many Legionella species and other Gammaproteobacteria. Regarding L. pneumophila virulence, our work showed that mutants for L. pneumophila T1SS (lssBD/tolC) were more disruptive to its virulence than lapG/lapD mutants. We also hypothesize, by challenging infection, that L. pneumophila might be actively targeting its host via RtxA. Additionally, by observing rtxA mutants as well as detecting RtxA on host surface briefly after inoculation and attenuating virulence by using anti RtxA antibodies, we assume an important but not limiting role for this protein in the infection process
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https://tel.archives-ouvertes.fr/tel-02900284
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Submitted on : Thursday, July 16, 2020 - 1:01:24 AM
Last modification on : Tuesday, July 21, 2020 - 4:46:38 PM

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  • HAL Id : tel-02900284, version 1

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Hussein Kanaan. Type 1 secretion system in Legionella pneumophila : substrate localization and role during the infectious cycle. Microbiology and Parasitology. Université de Lyon, 2019. English. ⟨NNT : 2019LYSE1090⟩. ⟨tel-02900284⟩

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