title: Pathogenic Rickettsia species acquire vitronectin from human serum to promote resistance to complement-mediated killing.
abstract: Bacteria of the genus Rickettsia are transmitted from arthropod vectors and primarily infect cells of the mammalian endothelial system. Throughout this infectious cycle, the bacteria are exposed to the deleterious effects of serum complement. Using Rickettsia conorii, the etiologic agent of Mediterranean spotted fever (MSF), as a model rickettsial species, we have previously demonstrated that this class of pathogen interacts with human factor H to mediate partial survival in human serum. Herein, we demonstrate that R. conorii also interacts with the terminal complement complex inhibitor vitronectin (Vn). We further demonstrate that an evolutionarily conserved rickettsial antigen, Adr1/RC1281, interacts with human vitronectin and is sufficient to mediate resistance to serum killing when expressed at the outer-membrane of serum sensitive Escherichia coli. Adr1 is an integral outer-membrane protein whose structure is predicted to contain eight membrane-embedded β-strands and four 'loop' regions that are exposed to extracellular milieu. Site-directed mutagenesis of Adr1 revealed that at least two predicted 'loop' regions are required to mediate resistance to complement-mediatedkilling and vitronectin acquisition. These results demonstrate that rickettsial species have evolved multiple mechanisms to evade complement deposition and that evasion of killing in serum is an evolutionarily conserved virulence attribute for this genus of obligate intracellular pathogens.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, IL, 60637, USA; Howard T. Ricketts Laboratory, Argonne, IL, 60439, USA; Vector-Borne Diseases Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, 70803, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Riley
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Patterson
authors.forename: Samantha
authors.initials: S
authors.lastname: Nava
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Martinez
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001770:Blood Bactericidal Activity; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016297:Mutagenesis, Site-Directed; D025941:Protein Interaction Mapping; D020114:Rickettsia conorii / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D019096:Vitronectin; D003165:Complement System Proteins