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Volume 56, Issue 4

Effect of deletion of the gene on virulence and vaccine potential of in mice Free

Abstract

undergoes an obligate flea–rodent–flea enzootic life cycle. The rapidly fatal properties of are responsible for the organism's sustained survival in natural plague foci. Lipopolysaccharide (LPS) plays several roles in 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. mutants were constructed with a deletion insertion in the 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 Δ mutants were then examined in a mouse model. The Δ mutation in a virulent strain led to no change in the LD value compared to that of the parental strain, while the Δ 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 (>0.05). The Δ 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 strains but there are potential improvements in the protective properties in attenuated vaccine strains.

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  • Accepted:
  • Published Online:
Keyword(s): CI, 95 % confidence interval , ESI FT-ICR, electrospray ionization Fourier transform ion cyclotron resonance , ImD50, 50 % immunizing dose , LAhexa, hexa-acyl lipid A , LAtetra, tetra-acyl lipid A and LPS, lipopolysaccharide
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2007-04-01
2024-04-25
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Effect of deletion of the lpxM gene on virulence and vaccine potential of Yersinia pestis in mice
J. Med. Microbiol. 56, 443 (2007); https://doi.org/10.1099/jmm.0.46880-0
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