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    Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus.

    Access Status
    Open access via publisher
    Authors
    Ulluwishewa, D.
    Wang, L.
    Pereira, C.
    Flynn, S.
    Cain, E.
    Stick, S.
    Reen, F.
    Ramsay, Joshua
    O'Gara, Fergal
    Date
    2016
    Type
    Journal Article
    
    Metadata
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    Citation
    Ulluwishewa, D. and Wang, L. and Pereira, C. and Flynn, S. and Cain, E. and Stick, S. and Reen, F. et al. 2016. Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus. Microbiology. 162: pp. 1398-1406.
    Source Title
    Microbiology
    DOI
    10.1099/mic.0.000317
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/47749
    Collection
    • Curtin Research Publications
    Abstract

    Aspiration of bile into the cystic fibrosis (CF) lung has emerged as a prognostic factor for reduced microbial lung biodiversity and the establishment of often fatal, chronic pathogen infections. Staphylococcus aureus is one of the earliest pathogens detected in the lungs of children with CF, and once established as a chronic infection, strategies for its eradication become limited. Several lung pathogens are stimulated to produce biofilms in vitro in the presence of bile. In this study, we further investigated the effects of bile on S. aureus biofilm formation. Most clinical S. aureus strains and the laboratory strain RN4220 were stimulated to form biofilms with sub-inhibitory concentrations of bile. Additionally, we observed bile-induced sensitivity to aminoglycosides, which we exploited in a bursa aurealis transposon screen to isolate mutants reduced in aminoglycoside sensitivity and augmented in bile-induced biofilm formation. We identified five mutants that exhibited hypersensitivity to bile with respect to bile-induced biofilm formation, three of which carried transposon insertions within gene clusters involved in wall teichoic acid (WTA) biosynthesis or transport. Strain TM4 carried an insertion between the divergently oriented tagH-tagG genes, encoding the putative WTA membrane translocation apparatus. Ectopic expression of tagG in TM4 restored a wild-type bile-induced biofilm response, suggesting that reduced translocation of WTA in TM4 induced sensitivity to bile and enhanced bile-induced biofilm formation. We propose that WTA may be important for protecting S. aureus against exposure to bile and that bile-induced biofilm formation may be an evolved response to protect cells from bile-induced cell lysis.

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