Phasevarion-regulated virulence in the emerging pediatric pathogen Kingella kingae

Yogitha N. Srikhanta, Ka Yee Fung, Georgina L. Pollock, Vicki Bennett-Wood, Benjamin P. Howden, Elizabeth L. Hartland

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Kingella kingae is a common etiological agent of pediatric osteoarticular infections. While current research has expanded our understanding of K. kingae pathogenesis, there is a paucity of knowledge about host-pathogen interactions and virulence gene regulation. Many host-adapted bacterial pathogens contain phase variable DNA methyltransferases (mod genes), which can control expression of a regulon of genes (phasevarion) through differential methylation of the genome. Here, we identify a phase variable type III mod gene in K. kingae, suggesting that phasevarions operate in this pathogen. Phylogenetic studies revealed that there are two active modK alleles in K. kingae. Proteomic analysis of secreted and surfaceassociated proteins, quantitative PCR, and a heat shock assay comparing the wildtype modK1 ON (i.e., in frame for expression) strain to a modK1 OFF (i.e., out of frame) strain revealed three virulence-associated genes under ModK1 control. These include the K. kingae toxin rtxA and the heat shock genes groEL and dnaK. Cytokine expression analysis showed that the interleukin-8 (IL-8), IL-1β, and tumor necrosis factor responses of THP-1 macrophages were lower in the modK1 ON strain than in the modK1::kan mutant. This suggests that the ModK1 phasevarion influences the host inflammatory response and provides the first evidence of this phase variable epigenetic mechanism of gene regulation in K. kingae.

Original languageEnglish
Article numbere00319-17
Number of pages15
JournalInfection and Immunity
Volume85
Issue number12
DOIs
Publication statusPublished - 2017

Keywords

  • Gene regulation
  • Kingella kingae
  • Phase variation
  • Phasevarion
  • Type III restrictionmodification systems

Cite this

Srikhanta, Yogitha N. ; Fung, Ka Yee ; Pollock, Georgina L. ; Bennett-Wood, Vicki ; Howden, Benjamin P. ; Hartland, Elizabeth L. / Phasevarion-regulated virulence in the emerging pediatric pathogen Kingella kingae. In: Infection and Immunity. 2017 ; Vol. 85, No. 12.
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Phasevarion-regulated virulence in the emerging pediatric pathogen Kingella kingae. / Srikhanta, Yogitha N.; Fung, Ka Yee; Pollock, Georgina L.; Bennett-Wood, Vicki; Howden, Benjamin P.; Hartland, Elizabeth L.

In: Infection and Immunity, Vol. 85, No. 12, e00319-17, 2017.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Phasevarion-regulated virulence in the emerging pediatric pathogen Kingella kingae

AU - Srikhanta, Yogitha N.

AU - Fung, Ka Yee

AU - Pollock, Georgina L.

AU - Bennett-Wood, Vicki

AU - Howden, Benjamin P.

AU - Hartland, Elizabeth L.

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