title: Evidence for a role of the polysaccharide capsule transport proteins in pertussis pathogenesis.
abstract: Polysaccharide (PS) capsules are important virulence determinants for many bacterial pathogens. Bordetella pertussis, the agent of whooping cough, produces a surface associated microcapsule but its role in pertussis pathogenesis remained unknown. Here we showed that the B. pertussis capsule locus is expressed in vivo in murine lungs and that absence of the membrane-associated protein KpsT, involved in the transport of the PS polymers across the envelope, but not the surface-exposed PS capsule itself, affects drastically B. pertussis colonization efficacy in mice. Microarray analysis revealed that absence of KpsT in B. pertussis resulted in global down-regulation of gene expression including key virulence genes regulated by BvgA/S, the master two-component system. Using a BvgS phase-locked mutant, we demonstrated a functional link between KpsT and BvgA/S-mediated signal transduction. Whereas pull-down assays do not support physical interaction between BvgS sensor and any of the capsule locus encoded proteins, absence of KpsT impaired BvgS oligomerization, necessary for BvgS function. Furthermore, complementation studies indicated that instead of KpsT alone, the entire PS capsule transport machinery spanning the cell envelope likely plays a role in BvgS-mediated signal transduction. Our work thus provides the first experimental evidence of a role for a virulence-repressed gene in pertussis pathogenesis.
authors.affiliation: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Science #03-05, 28 Medical Drive, Singapore 117597, Singapore.
authors.forename: Regina
authors.initials: R
authors.lastname: Hoo
authors.affiliation: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Science #03-05, 28 Medical Drive, Singapore 117597, Singapore.
authors.forename: Jian Hang
authors.initials: JH
authors.lastname: Lam
authors.affiliation: Transcriptomics and Applied Genomics, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille (CIIL), U1019, UMR8204, 1 rue du Professeur Calmette, F-59019 Lille, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Huot
authors.affiliation: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Science #03-05, 28 Medical Drive, Singapore 117597, Singapore.
authors.forename: Aakanksha
authors.initials: A
authors.lastname: Pant
authors.affiliation: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Science #03-05, 28 Medical Drive, Singapore 117597, Singapore.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Transcriptomics and Applied Genomics, Institut Pasteur de Lille, Centre for Infection and Immunity of Lille (CIIL), U1019, UMR8204, 1 rue du Professeur Calmette, F-59019 Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Hot
authors.affiliation: Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Centre for Life Science #03-05, 28 Medical Drive, Singapore 117597, Singapore.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Alonso
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001886:Bordetella pertussis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015536:Down-Regulation; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000378:metabolism*; D014917:Whooping Cough / Q000382:microbiology* / Q000473:pathology
chemical_list: D011135:Polysaccharides, Bacterial; D010566:Virulence Factors, Bordetella