title: Heme binding proteins of Bartonella henselae are required when undergoing oxidative stress during cell and flea invasion.
abstract: Bartonella are hemotropic bacteria responsible for emerging zoonoses. These heme auxotroph alphaproteobacteria must import heme for their growth, since they cannot synthesize it. To import exogenous heme, Bartonella genomes encode for a complete heme uptake system enabling transportation of this compound into the cytoplasm and degrading it to release iron. In addition, these bacteria encode for four or five outer membrane heme binding proteins (Hbps). The structural genes of these highly homologous proteins are expressed differently depending on oxygen, temperature and heme concentrations. These proteins were hypothesized as being 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 Hbps of Bartonella henselae, responsible for cat scratch disease. We show that Hbps can bind heme in vitro. They are able to enhance the efficiency of heme uptake when co-expressed with a heme transporter in Escherichia coli. Using B. henselae Hbp knockdown mutants, we show that these proteins are involved in defense against the oxidative stress, colonization of human endothelial cell and survival in the flea.
authors.affiliation: UMR BIPAR Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, INRA-Anses-UPEC-ENVA, Maisons-Alfort, France. fbiville@pasteur.fr
authors.forename: MaFeng
authors.initials: M
authors.lastname: Liu
authors.forename: Yann
authors.initials: Y
authors.lastname: Ferrandez
authors.forename: Emilie
authors.initials: E
authors.lastname: Bouhsira
authors.forename: Martine
authors.initials: M
authors.lastname: Monteil
authors.forename: Michel
authors.initials: M
authors.lastname: Franc
authors.forename: Henri-Jean
authors.initials: HJ
authors.lastname: Boulouis
authors.forename: Francis
authors.initials: F
authors.lastname: Biville
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018416:Bartonella henselae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003224:Congo Red / Q000378:metabolism; D042783:Endothelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006418:Heme / Q000378:metabolism; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D005423:Siphonaptera / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D016877:Oxidants; D020033:Protein Isoforms; D011994:Recombinant Proteins; D003224:Congo Red; D006418:Heme; D006861:Hydrogen Peroxide