The chromosomal SezAT toxin-antitoxin system promotes the maintenance of the SsPI-1 pathogenicity island in epidemic Streptococcus suis.

Abstract

Streptococcus suis has emerged as a causative agent of human meningitis and streptococcal toxic shock syndrome over the last years. The high pathogenicity of S. suis may be due in part to a laterally acquired pathogenicity island (renamed SsPI-1), which can spontaneously excise and transfer to recipients. Cells harboring excised SsPI-1 can potentially lose this island if cell division occurs prior to its reintegration; however, attempts to cure SsPI-1 from the host cells have been unsuccessful. Here, we report that an SsPI-1-borne Epsilon/Zeta toxin-antitoxin system (designated SezAT) promotes SsPI-1 stability in bacterial populations. The sezAT locus consists of two closely linked sezT and sezA genes encoding a toxin and its cognate antitoxin, respectively. Overproduction of SezT induces a bactericidal effect that can be neutralized by co-expression of SezA, but not by its later action. When devoid of a functional SezAT system, large-scale deletion of SsPI-1 is straightforward. Thus, SezAT serves to ensure inheritance of SsPI-1 during cell division, which may explain the persistence of epidemic S. suis. This report presents the first functional characterization of TA loci in S. suis, and the first biochemical evidence for the adaptive significance of the Epsilon/Zeta system in the evolution of pathogen virulence.