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Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella

Morreale, D. P.; Porsch, E. A.; Kern, B. K.; St. Geme, J. W.; Planet, P. J.

2022-11-28 microbiology
10.1101/2022.11.28.518221 bioRxiv
Show abstract

The Kingella genus includes two pathogenic species, namely K. kingae and K. negevensis, as well as strictly commensal species. Both K. kingae and K. negevensis secrete a toxin called RtxA that is absent in the commensal species. Phylogenetic analysis demonstrates that the toxin-encoding operon rtxCrtxAtolC was acquired by a common ancestor of the pathogenic Kingella species and that a preexisting type I secretion system was co-opted for toxin export. Subsequent genomic reorganization distributed the toxin machinery across two loci, with 30-35% of K. kingae strains containing two copies of the rtxA toxin gene. The rtxA duplication is largely clonal and strongly associated with invasive disease. In assays with isogenic strains, a single copy of rtxA was associated with reduced virulence in vitro. This study establishes the critical steps in the evolutionary transition from commensal to pathogen, including horizontal gene transfer, co-option of an existing secretion system, and gene duplication.

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