Differentialvasoproliferative traits of Bartonella henselae strains associated with autotransporter BafA variants

Bartonella henselae, a Gram-negative facultative intracellular bacterium, is the etiological agent of cat-scratch disease and also causes bacillary angiomatosis in immunocompromised individuals. Although the ability to promote vascular endothelial cell proliferation differsamong Bartonella species, variations among strains within B. henselae remain unclear. Bartonella angiogenic factor A (BafA) and Bartonella adhesin A (BadA) have been identifiedas autotransporters of B. henselae that are involved in endothelial cell proliferation. Although strain-specificdifferencesin the expression of BadA and the VirB/D4 type IV secretion system have been reported, BafA expression among B. henselae strains has yet to be examined. Therefore, the present study investigated the proliferation-promoting ability of 13 B. henselae strains from several sources in human umbilical vein endothelial cells (HUVECs). We identifiedBafA variants 1 and 2 based on the deduced amino acid sequences of its passenger domain. The recombinant proteins of both variants exhibited similar proliferation activity against HUVECs. However, BafA variant 2 strains showed cytotoxicity at a high bacterial inoculum in a direct coculture with HUVECs, which was attenuated in an indirect coculture. These strains, in contrast to BafA variant 1 strains, highly expressed BadA and exhibited bacterial aggregation. Based on a core genome SNP analysis of 50 B. henselae strains, the BafA variant types corresponded to clades 1-4. These results indicate that vasoproliferative traits differamong B. henselae clades based on the variant types. Therefore, this study provides a new conceptual framework in which the clades of B. henselae may predict their pathogenicity in humans.