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

The pathogenicity ofStenotrophomonas maltophiliais regulated in part by its quorum sensing (QS) system. The main QS signaling molecule inS. maltophiliais known as diffusible signal factor (DSF), and therpfgene cluster is responsible for its synthesis and perception. Two cluster variants have been previously described,rpf-1 andrpf-2, which differ basically in the conditions under which DSF is produced. Here, correlations between therpfvariant and antibiotic susceptibility, LPS electrophoretic profiles and virulence-related phenotypes were evaluated for a collection of 78 geographically and genetically diverse clinical strains ofS. maltophilia. In general there were associations between previously established genogroups and the genetic variant of therpfcluster. However, only few genotype-phenotype correlations could be observed. Resistance to the beta-lactam antibiotics ceftazidime and ticarcillin was associated with strains carrying therpf-1 variant, whereas strains of variantrpf-2, particularly those of genogroup C, showed higher resistance levels to colistin. Strains of variantrpf-2 were also significantly more virulent toGalleria mellonellalarvae than those ofrpf-1, most likely due to an increased ability ofrpf-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 inS. maltophiliarelated 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.