title: The smpB-ssrA mutant of Yersinia pestis functions as a live attenuated vaccine to protect mice against pulmonary plague infection.
abstract: The bacterial SmpB-SsrA system is a highly conserved translational quality control mechanism that helps maintain the translational machinery at full capacity. Here we present evidence to demonstrate that the smpB-ssrA genes are required for pathogenesis of Yersinia pestis, the causative agent of plague. We found that disruption of the smpB-ssrA genes leads to reduction in secretion of the type III secretion-related proteins YopB, YopD, and LcrV, which are essential for virulence. Consistent with these observations, the smpB-ssrA mutant of Y. pestis was severely attenuated in a mouse model of infection via both the intranasal and intravenous routes. Most significantly, intranasal vaccination of mice with the smpB-ssrA mutant strain of Y. pestis induced a strong antibody response. The vaccinated animals were well protected against subsequent lethal intranasal challenges with virulent Y. pestis. Taken together, our results indicate that the smpB-ssrA mutant of Y. pestis possesses the desired qualities for a live attenuated cell-based vaccine against pneumonic plague.
authors.affiliation: Center for Infectious Diseases and Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
authors.forename: Nihal A
authors.initials: NA
authors.lastname: Okan
authors.forename: Patricio
authors.initials: P
authors.lastname: Mena
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Benach
authors.forename: James B
authors.initials: JB
authors.lastname: Bliska
authors.forename: A Wali
authors.initials: AW
authors.lastname: Karzai
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics*; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D010930:Plague / Q000276:immunology* / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000276:immunology; D037521:Virulence Factors / Q000172:deficiency*; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014613:Vaccines, Attenuated; D037521:Virulence Factors; C078909:YopB protein, Yersinia; C078910:YopD protein, Yersinia