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

Abstract

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

Achromobacter xylosoxidans and Stenotrophomonas maltophilia: Emerging Pathogens Well-Armed for Life in the Cystic Fibrosis Patients’ Lung

“…The QS system is based on the diffusible signal factor (DSF), with cis-11-methyl-2-dodecenoic acid as the main signaling factor [ 167 ]. Its production is controlled by the rpf (regulation of pathogenicity factors) cluster, and two types of rpf clusters have been demonstrated in clinical strains: rpfF -1 (60%, 47 of 78 strains) and rpf -2 (40%, 31 of 78 strains), with established links between the type of DSF-based QS system and the phenotypes of biofilm formation, virulence, and antimicrobial resistance of the strains [ 168 , 169 ]. rpf -1-type Sm strains basically produce DSF in response to diverse environmental changes, whereas rpf -2-type Sm strains are deficient for basal DSF production while retaining their ability to detect DSF produced by other strains and subsequently produce DSF [ 168 ].…”

The Contribution of Efflux Systems to Levofloxacin Resistance in Stenotrophomonas maltophilia Clinical Strains Isolated in Warsaw, Poland

“…WP_180835982.1) with the same SmeRv amino acid sequence as Polish isolate no. 41/2011, was characterized by resistance to levofloxacin, colistin, ceftazidime, and ticarcillin-clavulanate, but there was no information concerning expression of the efflux system operon in PUC101 [ 51 ]. Besides that, only isolate no.…”

DSF-family quorum sensing signal-mediated intraspecies, interspecies, and inter-kingdom communication

“…Except for LeDSF, all DSFs are cis-2-unsaturated fatty acids containing fatty acid carbon chains of various lengths and cis double-bond configurations (Figure 1). Until now, DSF members have been detected in a range of Gram-negative bacterial species belonging to the γproteobacteria and β-proteobacteria groups, including Xanthomonas spp., Xylella fastidiosa, Stenotrophomonas maltophilia, Lysobacter enzymogenes and L. ferri philum and L. ferrooxidans, Burkholderia cenocepacia, Cronobacter turicensis, and Pseudomonas aeruginosa [7,[14][15][16][17][18][19][20][21]. In silico analysis suggests that Methylobacillus flagellates, Thiobacillus denitrificans, and bacteria in the genera Frateuria, Luteibacter, Pseudoxanthomonas, and Rhodanobacter also produce DSF.…”