Genetic Variants of the DSF Quorum Sensing System in Influence Virulence and Resistance Phenotypes Among Genotypically Diverse Clinical Isolates

The pathogenicity of is regulated in part by its quorum sensing (QS) system. The main QS signaling molecule in is known as diffusible signal factor (DSF), and the gene cluster is responsible for its synthesis and perception. Two cluster variants have been previously described, -1 and -2, which differ basically in the conditions under which DSF is produced. Here, correlations between the variant and antibiotic susceptibility, LPS electrophoretic profiles and virulence-related phenotypes were evaluated for a collection of 78 geographically and genetically diverse clinical strains of . In general there were associations between previously established genogroups and the genetic variant of the cluster. However, only few genotype-phenotype correlations could be observed. Resistance to the β-lactam antibiotics ceftazidime and ticarcillin was associated with strains carrying the -1 variant, whereas strains of variant -2, particularly those of genogroup C, showed higher resistance levels to colistin. Strains of variant -2 were also significantly more virulent to larvae than those of -1, most likely due to an increased ability of -2 strains to form biofilms. A comparative genomic analysis revealed the presence of proteins unique to individual genogroups. In particular, the strains of genogroup C share an operon that encodes for a new virulence determinant in related to the synthesis of an alternative Flp/Tad pilus. Overall, this study establishes a link between the DSF-based QS system and the virulence and resistance phenotypes in this species, and identifies potential high-risk clones circulating in European hospitals.