Pseudomonas aeruginosa Enolase Influences Bacterial Tolerance to Oxidative Stresses and Virulence.

Fei Chen,Xiaolei Pan,Ronghao Chen,Shouguang Jin,Yongxin Jin,Yiwei Liu,Chang Liu,Qiang Zhao,Zhihui Cheng,Yuding Weng,Weihui Wu

doi:10.3389/fmicb.2016.01999

Fei Chen, Xiaolei Pan + Show 9 more

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https://doi.org/10.3389/fmicb.2016.01999

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Abstract

Pseudomonas aeruginosa is a Gram negative opportunistic pathogenic bacterium, which causes acute and chronic infections. Upon entering the host, bacteria alter global gene expression to adapt to host environment and avoid clearance by the host. Enolase is a glycolytic enzyme involved in carbon metabolism. It is also a component of RNA degradosome, which is involved in RNA processing and gene regulation. Here, we report that enolase is required for the virulence of P. aeruginosa in a murine acute pneumonia model. Mutation of enolase coding gene (eno) increased bacterial susceptibility to neutrophil mediated killing, which is due to reduced tolerance to oxidative stress. Catalases and alkyl hydroperoxide reductases play a major role in protecting the cell from oxidative damages. In the eno mutant, the expression levels of catalases (KatA and KatB) were similar as those in the wild type strain in the presence of H2O2, however, the expression levels of alkyl hydroperoxide reductases (AhpB and AhpC) were significantly reduced. Overexpression of ahpB but not ahpC in the eno mutant fully restored the bacterial resistance to H2O2 as well as neutrophil mediated killing, and partially restored bacterial virulence in the murine acute pneumonia model. Therefore, we have identified a novel role of enolase in the virulence of P. aeruginosa.

Highlights

Pseudomonas aeruginosa is a ubiquitous Gram negative bacterium
Given that there was ∼104-fold difference in the bacterial load between wild type PAK and the eno mutant infected mice, it is likely that factors other than slow growth contribute to the reduced bacterial number in vivo
We show that enolase is required for the virulence of P. aeruginosa in a murine acute pneumonia model

Summary

Introduction

Pseudomonas aeruginosa is a ubiquitous Gram negative bacterium. It is a major cause of nosocomial infections, including severe burn infections, sepsis, urinary tract infection, and pneumonia. P. aeruginosa is the leading cause of chronic lung infection in cystic fibrosis (CF) patients and ventilator-associated pneumonia (VAP; Diaz et al, 2005; Mcbride, 2005). In a murine acute pneumonia model, it has been demonstrated that neutrophils are rapidly recruited to the lung in response to invading bacteria (Shaver and Hauser, 2004). Neutrophils are phagocytes that kill bacteria by generation of reactive oxygen species (ROS), phagocytosis, and degranulation (Ziltener et al, 2016)

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