Effect of deletion of the lpxM gene on virulence and vaccine potential of Yersinia pestis in mice.
Yersinia pestis undergoes an obligate flea-rodent-flea enzootic life cycle. The rapidly fatal properties of Y. pestis are responsible for the organism's sustained survival in natural plague foci. Lipopolysaccharide (LPS) plays several roles in Y. pestis pathogenesis, prominent among them being resistance to host immune effectors and induction of a septic-shock state during the terminal phases of infection. LPS is acylated with 4-6 fatty acids, the number varying with growth temperature and affecting the molecule's toxic properties. Y. pestis mutants were constructed with a deletion insertion in the lpxM gene in both virulent and attenuated strains, preventing the organisms from synthesizing the most toxic hexa-acylated lipid A molecule when grown at 25 degrees C. The virulence and/or protective potency of pathogenic and attenuated Y. pestis DeltalpxM mutants were then examined in a mouse model. The DeltalpxM mutation in a virulent strain led to no change in the LD(50) value compared to that of the parental strain, while the DeltalpxM mutation in attenuated strains led to a modest 2.5-16-fold reduction in virulence. LPS preparations containing fully hexa-acylated lipid A were ten times more toxic in actinomycin D-treated mice then preparations lacking this lipid A isoform, although this was not significant (P>0.05). The DeltalpxM mutation in vaccine strain EV caused a significant increase in its protective potency. These studies suggest there is little impact from lipid A modifications on the virulence of Y. pestis strains but there are potential improvements in the protective properties in attenuated vaccine strains.
Anisimov
Andrey P
AP
State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Moscow Region, Russia.
Shaikhutdinova
Rima Z
RZ
State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Moscow Region, Russia.
Pan'kina
Lyudmila N
LN
Russian Research Anti-Plague Institute 'Microbe', Saratov 410071, Russia.
Feodorova
Valentina A
VA
Russian Research Anti-Plague Institute 'Microbe', Saratov 410071, Russia.
Savostina
Elena P
EP
Russian Research Anti-Plague Institute 'Microbe', Saratov 410071, Russia.
Bystrova
Ol'ga V
OV
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia.
Lindner
Buko
B
Research Center Borstel, Leibniz Center for Medicine and Biosciences, D-23845 Borstel, Germany.
Mokrievich
Aleksandr N
AN
State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Moscow Region, Russia.
Bakhteeva
Irina V
IV
State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Moscow Region, Russia.
Titareva
Galina M
GM
State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Moscow Region, Russia.
Dentovskaya
Svetlana V
SV
State Research Center for Applied Microbiology and Biotechnology, Obolensk 142279, Moscow Region, Russia.
Kocharova
Nina A
NA
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia.
Senchenkova
Sof'ya N
SN
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia.
Holst
Otto
O
Research Center Borstel, Leibniz Center for Medicine and Biosciences, D-23845 Borstel, Germany.
Devdariani
Zurab L
ZL
Russian Research Anti-Plague Institute 'Microbe', Saratov 410071, Russia.
Popov
Yuriy A
YA
Russian Research Anti-Plague Institute 'Microbe', Saratov 410071, Russia.
Pier
Gerald B
GB
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston MA 02115, USA.
Knirel
Yuriy A
YA
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia.
D000818:Animals; D017353:Gene Deletion; D005798:Genes, Bacterial / Q000235:genetics; D008050:Lipid A / Q000235:genetics; D051379:Mice; D010930:Plague / Q000382:microbiology* / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D014774:Virulence / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*
D008050:Lipid A; D010931:Plague Vaccine