title: Polymorphisms in the lcrV gene of Yersinia enterocolitica and their effect on plague protective immunity.
abstract: Current efforts to develop plague vaccines focus on LcrV, a polypeptide that resides at the tip of type III secretion needles. LcrV-specific antibodies block Yersinia pestis type III injection of Yop effectors into host immune cells, thereby enabling phagocytes to kill the invading pathogen. Earlier work reported that antibodies against Y. pestis LcrV cannot block type III injection by Yersinia enterocolitica strains and suggested that lcrV polymorphisms may provide for escape from LcrV-mediated plague immunity. We show here that polyclonal or monoclonal antibodies raised against Y. pestis KIM D27 LcrV (LcrV(D27)) bind LcrV from Y. enterocolitica O:9 strain W22703 (LcrV(W22703)) or O:8 strain WA-314 (LcrV(WA-314)) but are otherwise unable to block type III injection by Y. enterocolitica strains. Replacing the lcrV gene on the pCD1 virulence plasmid of Y. pestis KIM D27 with either lcrV(W22703) or lcrV(WA-314) does not affect the ability of plague bacteria to secrete proteins via the type III pathway, to inject Yops into macrophages, or to cause lethal plague infections in mice. LcrV(D27)-specific antibodies blocked type III injection by Y. pestis expressing lcrV(W22703) or lcrV(WA-314) and protected mice against intravenous lethal plague challenge with these strains. Thus, although antibodies raised against LcrV(D27) are unable to block the type III injection of Y. enterocolitica strains, expression of lcrV(W22703) or lcrV(WA-314) in Y. pestis did not allow these strains to escape LcrV-mediated plague protective immunity in the intravenous challenge model.
authors.affiliation: Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, Illinois, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Miller
authors.forename: Lauriane E
authors.initials: LE
authors.lastname: Quenee
authors.forename: Derek
authors.initials: D
authors.lastname: Elli
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Ciletti
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D058947:Bacterial Secretion Systems; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology* / Q000382:microbiology; D010931:Plague Vaccine / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D016415:Sequence Alignment; D015008:Yersinia enterocolitica / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D058947:Bacterial Secretion Systems; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins