@article{mbs:/content/journal/jmm/10.1099/jmm.0.46880-0, author = "Anisimov, Andrey P. and Shaikhutdinova, Rima Z. and Pan'kina, Lyudmila N. and Feodorova, Valentina A. and Savostina, Elena P. and Bystrova, Ol'ga V. and Lindner, Buko and Mokrievich, Aleksandr N. and Bakhteeva, Irina V. and Titareva, Galina M. and Dentovskaya, Svetlana V. and Kocharova, Nina A. and Senchenkova, Sof'ya N. and Holst, Otto and Devdariani, Zurab L. and Popov, Yuriy A. and Pier, Gerald B. and Knirel, Yuriy A.", title = "Effect of deletion of the lpxM gene on virulence and vaccine potential of Yersinia pestis in mice", journal= "Journal of Medical Microbiology", year = "2007", volume = "56", number = "4", pages = "443-453", doi = "https://doi.org/10.1099/jmm.0.46880-0", url = "https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.46880-0", publisher = "Microbiology Society", issn = "1473-5644", type = "Journal Article", keywords = "ImD50, 50 % immunizing dose", keywords = "LAhexa, hexa-acyl lipid A", keywords = "LPS, lipopolysaccharide", keywords = "LAtetra, tetra-acyl lipid A", keywords = "ESI FT-ICR, electrospray ionization Fourier transform ion cyclotron resonance", keywords = "CI, 95 % confidence interval", abstract = " 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 °C. The virulence and/or protective potency of pathogenic and attenuated Y. pestis ΔlpxM mutants were then examined in a mouse model. The ΔlpxM mutation in a virulent strain led to no change in the LD50 value compared to that of the parental strain, while the ΔlpxM 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 ΔlpxM 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.", }