Virulent non-capsulate Yersinia pestis variants constructed by insertion mutagenesis

Area of Science:

• Microbiology
• Pathogen Biology
• Epidemiology

Background:

• Yersinia pestis causes plague, a zoonotic disease with significant public health implications.
• Understanding the genetic basis of Y. pestis virulence is crucial for controlling plague outbreaks.
• The role of specific virulence factors, such as the capsular antigen (FI) and murine toxin, in plague pathogenesis requires further elucidation.

Purpose of the Study:

• To generate and characterize Yersinia pestis mutants lacking specific virulence factors.
• To investigate the potential role of these mutants in natural plague foci and epizootic processes.
• To determine the impact of losing capsular antigen (FI) and/or murine toxin production on Y. pestis virulence.

Main Methods:

• Insertion mutagenesis using the plasmid pFS23 to create Y. pestis fra mutants.
• Assessment of pFra- strain production under non-selective conditions.
• Evaluation of virulence by determining LD50 values and survival duration in infected animals.

Main Results:

• Y. pestis variants lacking pFra (pFra-) can be generated at high frequency, potentially in natural plague foci.
• Loss of capsular antigen (FI) production alone, or in combination with absent murine toxin, did not increase LD50 values.
• Absence of FI antigen production led to prolonged survival of infected animals, suggesting a role in acute plague.
• The conversion of plague from acute to chronic forms may depend on host species and the parent Y. pestis strain.

Conclusions:

• Y. pestis pFra- strains may play a role in supporting epizootic processes.
• Previous reports of reduced virulence in Fra- strains may be due to confounding mutations.
• The capsular antigen (FI) appears to be a significant determinant of acute plague, while its absence may contribute to chronicity depending on host and strain factors.