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Volume 170, Issue 2

Mutation of , a -formyltransferase involved in O-antigen synthesis, results in biofilm formation, phase variation and attenuation in Open Access

Abstract

Two clinically important subspecies, subsp. (type A) and subsp. (type B) are responsible for most tularaemia cases, but these isolates typically form a weak biofilm under conditions. Phase variation of the lipopolysaccharide (LPS) has been reported in these subspecies, but the role of variation is unclear as LPS is crucial for virulence. We previously demonstrated that a subpopulation of LPS variants can constitutively form a robust biofilm but it is unclear whether virulence was affected. In this study, we show that biofilm-forming variants of both fully virulent subspecies were highly attenuated in the murine tularaemia model by multiple challenge routes. Genomic sequencing was performed on these strains, which revealed that all biofilm-forming variants contained a lesion within the gene, a formyltransferase involved in O-antigen synthesis. A Δ deletion mutant recapitulated the biofilm, O-antigen and virulence phenotypes observed in natural variants and could be rescued through complementation with a functional gene. Since the spontaneously derived biofilm-forming isolates in this study were a subpopulation of natural variants, reversion events to the gene were detected that eliminated the phenotypes associated with biofilm variants and restored virulence. These results demonstrate a role for WbtJ in biofilm formation, LPS variation and virulence of .

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): biofilm , Francisella tularensis , LPS , O-antigen , phase variation , SNP reversion , tularaemia , virulence and WbtJ
Funding
This study was supported by the:
  • Defense Threat Reduction Agency (Award CB10477)
    • Principle Award Recipient: JoelA. Bozue
  • Defense Threat Reduction Agency (Award CB10645)
    • Principle Award Recipient: JoelA. Bozue
© Microbiology Society
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2024-02-29
2024-05-20
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Mutation of wbtJ, a N-formyltransferase involved in O-antigen synthesis, results in biofilm formation, phase variation and attenuation in Francisella tularensis
Microbiology 170, 001437 (2024); https://doi.org/10.1099/mic.0.001437
/content/journal/micro/10.1099/mic.0.001437
/content/journal/micro/10.1099/mic.0.001437
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