Role of BordetellaO Antigen in Respiratory Tract Infection

ABSTRACTLipopolysaccharide (LPS), as the major surface molecule of gram-negative bacteria, interacts with the host in complex ways, both inducing and protecting against aspects of inflammatory and adaptive immunity. The membrane-distal repeated carbohydrate structure of LPS, the O antigen, can prevent antibody functions and may vary as a mechanism of immune evasion. Genes of the wbmlocus are required for the assembly of O antigen on the animal pathogen Bordetella bronchisepticaand the human pathogen B. parapertussis. However, the important human pathogen B. pertussislacks these genes and a number of in vitro and in vivo characteristics associated with O antigen in other organisms. To determine the specific functions of O antigen in these closely related Bordetellasubspecies, we compared wbmdeletion (Δwbm) mutants of B. bronchisepticaand B. parapertussisin a variety of assays relevant to natural respiratory tract infection. Complement was not activated or depleted by wild-type bordetellae expressing O antigen, but both Δwbmmutants activated complement and were highly sensitive to complement-mediated killing in vitro. Although the O-antigen structures appear to be substantially similar, the two mutants differed strikingly in their defects within the respiratory tract. The B. parapertussisΔwbmmutant was severely defective in colonization of the tracheas and lungs of mice, while the B. bronchisepticaΔwbmmutant showed almost no defect. While in vitro characteristics such as serum resistance may be attributable to O antigen directly, the role of O antigen during infection appears to be more complex, possibly involving factors differing among the closely related bordetellae or different interactions between each one and its host.