Pouring Salt on a Wound: Pseudomonas aeruginosa Virulence Factors Alter Na+ and Cl- Flux in the Lung

Abstract

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen with multiple niches in the human body, including the lung. P. aeruginosa infections are particularly damaging or fatal for patients with ventilator-associated pneumonia, chronic obstructive pulmonary disease, and cystic fibrosis (CF). To establish an infection, P. aeruginosa relies on a suite of virulence factors, including lipopolysaccharide, phospholipases, exoproteases, phenazines, outer membrane vesicles, type III secreted effectors, flagella, and pili. These factors not only damage the epithelial cell lining but also induce changes in cell physiology and function such as cell shape, membrane permeability, and protein synthesis. While such virulence factors are important in initial infection, many become dysregulated or nonfunctional during the course of chronic infection. Recent work on the virulence factors alkaline protease (AprA) and CF transmembrane conductance regulator inhibitory factor (Cif) show that P. aeruginosa also perturbs epithelial ion transport and osmosis, which may be important for the long-term survival of this microbe in the lung. Here we discuss the literature regarding host physiology-altering virulence factors with a focus on Cif and AprA and their potential roles in chronic infection and immune evasion.

Phage Therapy: a Step Forward in the Treatment of Pseudomonas aeruginosa Infections

“…aeruginosa possesses an arsenal of virulence factors enabling it to invade host cells and circumvent host defenses (35,42). These mechanisms of virulence include secreted factors such as proteases, elastase, pyocyanin, exotoxin A, phospholipase C, and exoenzyme S and also cell-associated factors such as lipopolysaccharide (LPS), flagella, and pili (35,43).…”

Database on the taxonomical characterisation and potential toxigenic capacities of microorganisms used for the industrial production of food enzymes and feed additives, which do not have a recommendation for Qualified Presumption of Safety

“…Phenazines display a broad spectrum of (toxic) activity toward prokaryotic and eukaryotic organisms, varying according to the nature and position of the substituent on the heterocyclic ring. They are considered as virulent factor pf P. aeruginosa (Ballok and O'Toole, 2013), but no standard toxicity data have been found in this report for these substances. Phenazines are considered redox-active compounds as well as a cytotoxic pigment.…”

“…They are considered as virulent factor pf P. aeruginosa (Ballok and O'Toole, 2013), but no standard toxicity data have been found in this report for these substances. Phenazines are considered redox-active compounds as well as a cytotoxic pigment.…”

Rational Design of Potent and Selective Inhibitors of an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa

“…3 P. aeruginosa secretes the CFTR inhibitory factor (Cif) that blocks the post-endocytic deubiquitination of CFTR and thus facilitates its lysosomal degradation. 4 Cif is a member of the α/β hydrolase family and has demonstrated epoxide hydrolase (EH) activity. 5 Using site directed mutations and inhibitors, we observed that Cif EH activity is critical for the inhibition of CFTR deubiquitination.…”