• Open Access

Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis

Authors

  • Christophe Bordi,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Marie-Cécile Lamy,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Isabelle Ventre,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Elise Termine,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Abderrahman Hachani,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
    2. Imperial College London, Division of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, South Kensington Campus, Flowers Building, London SW7 2AZ, UK.
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  • Sandy Fillet,

    1. Imperial College London, Division of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, South Kensington Campus, Flowers Building, London SW7 2AZ, UK.
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    • Present address: Consejo Superior de Investigaciones Científicas, Estación Experimental del Zaidín, Department of Environmental Protection, C/ Prof Albareda, 1, E-18008 Granada, Spain.

  • Béatrice Roche,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Sophie Bleves,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Vincent Méjean,

    1. Laboratoire de Chimie Bactérienne, UPR9043, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Andrée Lazdunski,

    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
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  • Alain Filloux

    Corresponding author
    1. Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UPR9027, CNRS-IMM, Université de la Méditerranée, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
    2. Imperial College London, Division of Cell and Molecular Biology, Centre for Molecular Microbiology and Infection, South Kensington Campus, Flowers Building, London SW7 2AZ, UK.
      E-mail a.filloux@imperial.ac.uk; Tel. (+44) 0 20 7594 9651; Fax (+44) 0 20 7594 3069.
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E-mail a.filloux@imperial.ac.uk; Tel. (+44) 0 20 7594 9651; Fax (+44) 0 20 7594 3069.

Summary

Bacterial pathogenesis often depends on regulatory networks, two-component systems and small RNAs (sRNAs). In Pseudomonas aeruginosa, the RetS sensor pathway downregulates expression of two sRNAs, rsmY and rsmZ. Consequently, biofilm and the Type Six Secretion System (T6SS) are repressed, whereas the Type III Secretion System (T3SS) is activated. We show that the HptB signalling pathway controls biofilm and T3SS, and fine-tunes P. aeruginosa pathogenesis. We demonstrate that RetS and HptB intersect at the GacA response regulator, which directly controls sRNAs production. Importantly, RetS controls both sRNAs, whereas HptB exclusively regulates rsmY expression. We reveal that HptB signalling is a complex regulatory cascade. This cascade involves a response regulator, with an output domain belonging to the phosphatase 2C family, and likely an anti-anti-σ factor. This reveals that the initial input in the Gac system comes from several signalling pathways, and the final output is adjusted by a differential control on rsmY and rsmZ. This is exemplified by the RetS-dependent but HptB-independent control on T6SS. We also demonstrate a redundant action of the two sRNAs on T3SS gene expression, while the impact on pel gene expression is additive. These features underpin a novel mechanism in the fine-tuned regulation of gene expression.

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