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.