Higher Prevalence of PldA, a Pseudomonas aeruginosa Trans-Kingdom H2-Type VI Secretion System Effector, in Clinical Isolates Responsible for Acute Infections and in Multidrug Resistant Strains.

Thibaud Boulant,Yves-Marie Boudehen,Laurent Dortet,Thierry Naas,Patrick Plesiat,Alain Filloux

doi:10.3389/fmicb.2018.02578

Abstract

Pseudomonas aeruginosa can manipulate eukaryotic host cells using secreted effectors delivered by the type III or the type VI Secretion Systems (T3SS and T6SS). The T3SS allows the injection of bacterial effectors (Exo toxins) into eukaryotic cell. P. aeruginosa, encodes three T6SSs, H1-, H2- and H3-T6SS. The H1-T6SS is mainly involved in delivering toxins to kill bacterial competitors. Recently, two T6SS-secreted phospholipases D, PldA (H2-T6SS) and PldB (H3-T6SS), were identified as trans-kingdom virulence effectors, triggering both killing of bacterial competitors and internalization into non-phagocytic cells. We deciphered the prevalence of T3SS and T6SS effectors encoding genes in 185 clinical isolates responsible for infections (septicaemia, pulmonary infections, urinary tract infections, and chronic infections in CF patients), 47 environmental strains, and on 33 carbapenemase-producers. We included 107 complete genomes of P. aeruginosa available in public databases. The prevalence of pldA is increased in clinical isolates responsible for severe acute infection and particularly in multi-drug resistant strains. In contrast, the pldB prevalence was high (96.8%) in all isolates. Regarding T3SS effectors, exoT and exoY are present in nearly all isolates while exoS and exoU were found to be exclusive with a higher prevalence of exoU+ strains in severe acute infections. The hypervirulent exoU+ isolates are more prone to be pldA+, suggesting a role of PldA in virulence. Finally, we observed that extremely drug resistant isolates producing an IMP-type carbapenemase were all pldA+. Our results suggest that PldA might have a role during pulmonary infections and have been co-selected in multidrug resistant strains particularly IMP-producers.

Highlights

Pseudomonas aeruginosa is an extracellular Gram-negative bacterium responsible for more than 51,000 healthcare associated infections per year in the United States according to Centers for Disease Control and Prevention (2013)
Our results confim those of a very recent study which reports that the presence of pldA and exoU in mucoid P. aeruginosa is associated with high risk of exacerbations in non-cystic fibrosis (CF) patients (Luo et al, 2018)
Since it has been demonstrated that PldA is a trans-kingdom T6SS effector that allows P. aeruginosa to interact with epithelial cells (Jiang et al, 2014; Hachani et al, 2016), we might hypothesize that the worst outcome observed with exoU+ isolates might depend on the expression of pldA, at least partially

Summary

Introduction

Pseudomonas aeruginosa is an extracellular Gram-negative bacterium responsible for more than 51,000 healthcare associated infections per year in the United States according to Centers for Disease Control and Prevention (2013). P. aeruginosa related-infections are mostly healthcare associated and cause a large subset of diseases including urinary tract infections (UTIs), acute pulmonary infections, wound infections, acute otitis and septicaemia (Stryjewski and Sexton, 2003) It is a major cause of chronic infection in patients with cystic fibrosis (CF) (Lund-Palau et al, 2016). PldA and PldB have been proposed to be secreted via H2- and H3-T6SS, respectively (Russell et al, 2013; Jiang et al, 2014; Hachani et al, 2016) These two virulence factors are encoded in two distinct pld clusters that are not present in all P. aeruginosa isolates (Wilderman et al, 2001)

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