title: The rickettsial OmpB β-peptide of Rickettsia conorii is sufficient to facilitate factor H-mediated serum resistance.
abstract: Pathogenic species of the spotted fever group Rickettsia are subjected to repeated exposures to the host complement system through cyclic infections of mammalian and tick hosts. The serum complement machinery is a formidable obstacle for bacteria to overcome if they endeavor to endure this endozoonotic cycle. We have previously demonstrated that that the etiologic agent of Mediterranean spotted fever, Rickettsia conorii, is susceptible to complement-mediated killing only in the presence of specific monoclonal antibodies. We have also shown that in the absence of particular neutralizing antibody, R. conorii is resistant to the effects of serum complement. We therefore hypothesized that the interactions between fluid-phase complement regulators and conserved rickettsial outer membrane-associated proteins are critical to mediate serum resistance. We demonstrate here that R. conorii specifically interacts with the soluble host complement inhibitor, factor H. Depletion of factor H from normal human serum renders R. conorii more susceptible to C3 and membrane attack complex deposition and to complement-mediated killing. We identified the autotransporter protein rickettsial OmpB (rOmpB) as a factor H ligand and further demonstrate that the rOmpB β-peptide is sufficient to mediate resistance to the bactericidal properties of human serum. Taken together, these data reveal an additional function for the highly conserved rickettsial surface cell antigen, rOmpB, and suggest that the ability to evade complement-mediated clearance from the hematogenous circulation is a novel virulence attribute for this class of pathogens.
authors.affiliation: University of Chicago, Department of Microbiology, Chicago, Illinois, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Riley
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Patterson
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Martinez
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane; D017242:Complement Factor H / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits; D020114:Rickettsia conorii / Q000235:genetics / Q000276:immunology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008024:Ligands; D021122:Protein Subunits; D017242:Complement Factor H