Serendipitous Discovery of an Immunoglobulin-binding Autotransporter in Bordetella

Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9610

^* To whom correspondence should be addressed. Email: cotter{at}lifesci.ucsb.edu.

	Abstract

We describe the serendipitous discovery of BatB, a classical-type Bordetella autotransporter (AT) protein with an 180 kDa passenger domain that remains non-covalently associated with the outer membrane. Like genes encoding all characterized protein virulence factors in Bordetella, batB transcription is positively regulated by the master virulence regulatory system BvgAS. BatB is predicted to share similarity with IgA proteases and we showed that BatB binds immunoglobulin in vitro. In vivo, a B. bronchiseptica batB mutant was unable to overcome innate immune defenses and was cleared from the lower respiratory tracts of mice more rapidly than wild type B. bronchiseptica. This defect was abrogated in SCID mice, suggesting that BatB functions to resist clearance during the first week post-inoculation in a manner dependent on B and T cell-mediated activities. Together with the previous demonstration that polymorphonuclear neutrophils (PMN) are critical for control of B. bronchiseptica in mice, our data support the hypothesis that BatB prevents non-specific antibodies from facilitating PMN-mediated clearance during the first few days post-inoculation. Neither of the strictly human-adapted Bordetella subspecies produces a fully functional BatB protein; nucleotide differences within the putative promoter region prevent batB transcription in B. pertussis, and although expressed, the batB gene of B. parapertussis_hu contains a large in-frame deletion relative to batB of B. bronchiseptica. Together, our data suggest that BatB played an important role in the evolution of virulence and host-specificity amongst the mammalian-adapted bordetellae.