Autoinducer-2 Facilitates Pseudomonas aeruginosa PAO1 Pathogenicity in Vitro and in Vivo.

Hongdong Li,Jialin Yu,Xingyuan Li,Zhengli Wang,Hong Wei,Chao Song,Yunhui Zhang,Zhenqiu Liu

doi:10.3389/fmicb.2017.01944

Abstract

Bacterial communication systems, such as quorum sensing (QS), have provided new insights of alternative approaches in antimicrobial treatment. We recently reported that one QS signal, named as autoinducer-2 (AI-2), can affect the behaviors of Pseudomonas aeruginosa PAO1 in a dose-dependent manner. In this study, we aimed to investigate the effects of AI-2 on P. aeruginosa PAO1 biofilm formation and virulence factors production in vitro, and in vivo using a pulmonary infection mouse model. Exogenous AI-2 resulted in increased biofilms architecture, the number of viable cells, and the yield of pyocyanin and elastase virulence factors in wild type P. aeruginosa PAO1. However, no such effect was observed in P. aeruginosa lasR rhlR mutant strain. In vivo, the use of AI-2 significantly increased the mortality, lung bacterial count and histological lung damage of mice with acute P. aeruginosa PAO1 infection. Our data suggest that AI-2 promotes the formation of P. aeruginosa PAO1 biofilms and the production of virulence factors by interfering with P. aeruginosa QS systems, resulting in decreased host survival. AI-2 may be a therapeutic target for the clinical treatment of a co-infection of P. aeruginosa and AI-2 producing bacteria.

Highlights

Pseudomonas aeruginosa is a versatile pathogenic bacterium, which is relevant to various acute and chronic infections in immunocompromised patients, such as those with cystic fibrosis, third-degree burns, and implanted medical devices (Mathee et al, 2008; Silby et al, 2011; Gellatly and Hancock, 2013)
We aimed to investigate the effects of AI-2 on P. aeruginosa biofilm formation and virulence factors production in vitro, as well as in vivo using a pulmonary infection mouse model, and to explore the roles of AI-2 in P. aeruginosa infections
AI-2 producing S. mitis and Klebsiella pneumoniae were the most frequent microbes in the biofilms on the surface of neonatal endotracheal tubes extubated from mechanically ventilated newborns, and the AI-2 concentration secreted by these AI-2 producing bacteria in the biofilms on the surface of neonatal endotracheal tubes was about 10–50 nM (Li et al, 2015b; Wang et al, 2016; Pan et al, 2017)

Summary

Introduction

Pseudomonas aeruginosa is a versatile pathogenic bacterium, which is relevant to various acute and chronic infections in immunocompromised patients, such as those with cystic fibrosis, third-degree burns, and implanted medical devices (Mathee et al, 2008; Silby et al, 2011; Gellatly and Hancock, 2013). The QS signaling molecules mainly contain two parts, Autoinducer-2 Facilitates Pseudomonas aeruginosa PAO1 Pathogenicity oligopeptides are commonly secreted by Gram-positive bacteria, while N-acyl homoserine lactones are commonly secreted by Gram-negative bacteria (Miller and Bassler, 2001). Acyl homoserine lactone (AHL)-based QS systems in P. aeruginosa mainly involves the las and rhl systems, which encodes two specific signal molecules named N-(3-oxododecanoyl)L-homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-Lhomoserine lactone (C4-HSL), respectively (Pearson et al, 1994; Ochsner and Reiser, 1995; Miller and Bassler, 2001). Researchers found that P. aeruginosa employs the Pseudomonas quinolone signal (PQS) system, which can control the rhl system activation (Diggle et al, 2003)

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