Bartonellae are hemotropic bacteria, agents responsible for emerging zoonoses. These Alphaproteobacteria are heme auxotroph which must import heme for supporting their growth, as they cannot synthesize it. Therefore, Bartonella genome encodes for a complete heme uptake system allowing the transportation of this compound in the cytoplasm. Heme has also been shown to be used as an iron source for Bartonella. Similarly to other bacteria which use heme as an iron source, Bartonellae must degrade it to allow the release of iron. For Bartonella, the genes cluster devoted to the heme uptake system contains a gene encoding for a polypeptide that shares homologies with heme trafficking or degrading enzymes. Using complementation of an E. coli mutant strain impaired in heme degradation, we demonstrated that HemS from Bartonella henselae allows the release of iron from heme. Recombinant HemS of B. henselae binds heme and can degrade it in the presence of a suitable electron donor. Knocking down the expression of HemS in B. henselae reduces B. henselae ability to face H2O2 exposure. Bartonellae encode for four or five outer membrane Heme binding proteins. The structural genes of these highly homologous proteins are expressed differently according to oxygen, temperature, and heme concentration. These proteins were hypothesized to be involved in various cellular processes according to their ability to bind heme and their regulation profile. In this report, we investigated the roles of the four Heme binding proteins of Bartonella henselae. We show that these proteins are involved in the defense against oxidative stress, colonization of endothelial cells and survival inside the flea
