• Open Access

A bile-inducible membrane protein mediates bifidobacterial bile resistance

Authors

  • Lorena Ruiz,

    1. Departamento de Microbiología y Bioquímica de Productos Lácteos, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, Spain
    2. Department of Microbiology and Alimentary Pharmabiotic Centre, University College of Cork, Cork, Ireland
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  • Mary O'Connell-Motherway,

    1. Department of Microbiology and Alimentary Pharmabiotic Centre, University College of Cork, Cork, Ireland
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  • Aldert Zomer,

    1. Department of Microbiology and Alimentary Pharmabiotic Centre, University College of Cork, Cork, Ireland
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    • Present address: Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

  • Clara G. de los Reyes-Gavilán,

    1. Departamento de Microbiología y Bioquímica de Productos Lácteos, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, Spain
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  • Abelardo Margolles,

    1. Departamento de Microbiología y Bioquímica de Productos Lácteos, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, Spain
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  • Douwe van Sinderen

    Corresponding author
    1. Department of Microbiology and Alimentary Pharmabiotic Centre, University College of Cork, Cork, Ireland
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E-mail d.vansinderen@ucc.ie; Tel. (+353) 21 490 1365; Fax (+353) 21 490 3101.

Summary

Bbr_0838 from Bifidobacterium breve UCC2003 is predicted to encode a 683 residue membrane protein, containing both a permease domain that displays similarity to transporters belonging to the major facilitator superfamily, as well as a CBS (cystathionine beta synthase) domain. The high level of similarity to bile efflux pumps from other bifidobacteria suggests a significant and general role for Bbr_0838 in bile tolerance. Bbr_0838 transcription was shown to be monocistronic and strongly induced upon exposure to bile. Further analysis delineated the transcriptional start site and the minimal region required for promoter activity and bile regulation. Insertional inactivation of Bbr_0838 in B. breve UCC2003 resulted in a strain, UCC2003:838800, which exhibited reduced survival upon cholate exposure as compared with the parent strain, a phenotype that was reversed when a functional, plasmid-encoded Bbr_0838 gene was introduced into UCC2003:838800. Transcriptome analysis of UCC2003:838800 grown in the presence or absence of bile demonstrated that transcription of Bbr_0832, which is predicted to encode a macrolide efflux transporter gene, was significantly increased in the presence of bile, representing a likely compensatory mechanism for bile removal in the absence of Bbr_0838. This study represents the first in-depth analysis of a bile-inducible locus in bifidobacteria, identifying a key gene relevant for bifidobacterial bile tolerance.

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