title: BipA Is Associated with Preventing Autoagglutination and Promoting Biofilm Formation in Bordetella holmesii.
abstract: Bordetella holmesii causes both invasive and respiratory diseases in humans. Although the number of cases of pertussis-like respiratory illnesses due to B. holmesii infection has increased in the last decade worldwide, little is known about the virulence factors of the organism. Here, we analyzed a B. holmesii isolate that forms large aggregates and precipitates in suspension, and subsequently demonstrated that the autoagglutinating isolate is deficient in Bordetella intermediate protein A (BipA) and that this deletion is caused by a frame-shift mutation in the bipA gene. A BipA-deficient mutant generated by homologous recombination also exhibited the autoagglutination phenotype. Moreover, the BipA mutant adhered poorly to an abiotic surface and failed to form biofilms, as did two other B. holmesii autoagglutinating strains, ATCC 51541 and ATCC 700053, which exhibit transcriptional down-regulation of bipA gene expression, indicating that autoagglutination indirectly inhibits biofilm formation. In a mouse intranasal infection model, the BipA mutant showed significantly lower levels of initial lung colonization than did the parental strain (P < 0.01), suggesting that BipA might be a critical virulence factor in B. holmesii respiratory infection. Together, our findings suggest that BipA production plays an essential role in preventing autoagglutination and indirectly promoting biofilm formation by B. holmesii.
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hiramatsu
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Otsuka
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Shibayama
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kamachi
mesh_terms: D000371:Agglutination / Q000235:genetics*; D000372:Agglutination Tests; D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018441:Biofilms; D001884:Bordetella / Q000502:physiology*; D001885:Bordetella Infections / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000382:microbiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; C420027:BipA protein, Bordetella