AUTHOR=Yero Daniel , Huedo Pol , Conchillo-Solé Oscar , Martínez-Servat Sònia , Mamat Uwe , Coves Xavier , Llanas Ferran , Roca Ignasi , Vila Jordi , Schaible Ulrich E. , Daura Xavier , Gibert Isidre 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01160

DOI=10.3389/fmicb.2020.01160

ISSN=1664-302X

ABSTRACT=<p>The pathogenicity of <italic>Stenotrophomonas maltophilia</italic> is regulated in part by its quorum sensing (QS) system. The main QS signaling molecule in <italic>S. maltophilia</italic> is known as diffusible signal factor (DSF), and the <italic>rpf</italic> gene cluster is responsible for its synthesis and perception. Two cluster variants have been previously described, <italic>rpf</italic>-1 and <italic>rpf</italic>-2, which differ basically in the conditions under which DSF is produced. Here, correlations between the <italic>rpf</italic> 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 <italic>S. maltophilia</italic>. In general there were associations between previously established genogroups and the genetic variant of the <italic>rpf</italic> 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 <italic>rpf</italic>-1 variant, whereas strains of variant <italic>rpf</italic>-2, particularly those of genogroup C, showed higher resistance levels to colistin. Strains of variant <italic>rpf</italic>-2 were also significantly more virulent to <italic>Galleria mellonella</italic> larvae than those of <italic>rpf</italic>-1, most likely due to an increased ability of <italic>rpf</italic>-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 <italic>S. maltophilia</italic> 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.</p>