Trimeric autotransporter adhesins (TAAs) are a major class of proteins by which pathogenic proteobacteria adhere to their hosts. Prominent examples include Yersinia YadA, Haemophilus Hia and Hsf, Moraxella UspA1 and A2, and Neisseria NadA. TAAs also occur in symbiotic and environmental species and presumably represent a general solution to the problem of adhesion in proteobacteria. The general structure of TAAs follows a head-stalk-anchor architecture, where the heads are the primary mediators of attachment and autoagglutination. In the major adhesin of Bartonella henselae, BadA, the head consists of three domains, the N-terminal of which shows strong sequence similarity to the head of Yersinia YadA. The two other domains were not recognizably similar to any protein of known structure. We therefore determined their crystal structure to a resolution of 1.1 Å. Both domains are β-prisms, the N-terminal one formed by interleaved, five-stranded β-meanders parallel to the trimer axis and the C-terminal one by five-stranded β-meanders orthogonal to the axis. Despite the absence of statistically significant sequence similarity, the two domains are structurally similar to domains from Haemophilus Hia, albeit in permuted order. Thus, the BadA head appears to be a chimera of domains seen in two other TAAs, YadA and Hia, highlighting the combinatorial evolutionary strategy taken by pathogens.
The ability to adhere is an important aspect of the interaction between bacteria and their environment. Adhesion allows them to aggregate into colonies, form biofilms with other species, and colonize surfaces. Where the surfaces are provided by other organisms, adhesion can lead to a wide range of outcomes, from symbiosis to pathogenicity. In Proteobacteria, colonization of the host depends on a wide range of adhesive surface molecules, among which Trimeric Autotransporter Adhesins (TAAs) represent a major class. In electron micrographs, TAAs resemble lollipops projecting from the bacterial surface, and in all investigated cases, the adhesive properties reside in their heads. We have determined the head structure of BadA, the major adhesin of Bartonella henselae. This pathogen causes cat scratch disease in humans, but can lead to much more severe disease in immunosuppressed patients, e.g., during chemotherapy or after HIV infection. Surprisingly, domains previously seen in other TAA heads are combined in a novel assembly, illustrating how pathogens rearrange available building blocks to create new adhesive surface molecules.