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

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

doi:10.3389/fmicb.2020.01160

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.

Highlights

Stenotrophomonas maltophilia are metabolically and genetically diverse Gram-negative bacilli belonging to the γ-proteobacteria class that inhabit a wide range of environmental niches, mainly in association with plant rhizospheres (Ryan et al, 2009; Brooke, 2012)
To deepen the knowledge and understanding of the resistance and virulence phenotypes displayed by S. maltophilia, in a way that is consistent with this high-diversity context, we have studied a panel of genetically diverse clinical S. maltophilia isolates with focus on the two genetic variants of the diffusible signal factor (DSF)-mediated quorum sensing (QS) system
This study shows that the QS system plays a pivotal role in pathogenicity and persistence in S. maltophilia

Summary

Introduction

Stenotrophomonas maltophilia are metabolically and genetically diverse Gram-negative bacilli belonging to the γ-proteobacteria class that inhabit a wide range of environmental niches, mainly in association with plant rhizospheres (Ryan et al, 2009; Brooke, 2012). S. maltophilia show low susceptibility to many antibiotics, including those commonly used to treat infections by Gramnegative opportunistic pathogens (Sánchez, 2015) Have they a variety of intrinsic resistance mechanisms affecting almost all antibiotic classes but they are able to acquire new resistances via horizontal gene transfer and mutations. The phenomenon of heteroresistance has been described in S. maltophilia as a mechanism to withstand antibiotic treatment (Martínez-Servat et al, 2018) For these reasons, this species has been classified as one of the leading multidrug resistant (MDR) organisms in hospital settings (Brooke, 2014) and has been included in the global priority list of the top 10 resistant microorganisms (TOTEM) isolated in ICUs (Rello et al, 2019)

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