Pseudomonas aeruginosa: breaking down barriers

Abstract

Many bacterial pathogens have evolved ingenious ways to escape from the lung during pneumonia to cause bacteremia. Unfortunately, the clinical consequences of this spread to the bloodstream are frequently dire. It is therefore important to understand the molecular mechanisms used by pathogens to breach the lung barrier. We have recently shown that Pseudomonas aeruginosa, one of the leading causes of hospital-acquired pneumonia, utilizes the type III secretion system effector ExoS to intoxicate pulmonary epithelial cells. Injection of these cells leads to localized disruption of the pulmonary-vascular barrier and dissemination of P. aeruginosa to the bloodstream. We put these data in the context of previous studies to provide a holistic model of P. aeruginosa dissemination from the lung. Finally, we compare P. aeruginosa dissemination to that of other bacteria to highlight the complexity of bacterial pneumonia. Although respiratory pathogens use distinct and intricate strategies to escape from the lungs, a thorough understanding of these processes can lay the foundation for new therapeutic approaches for bacterial pneumonia.

Keywords: Bacterial dissemination; ExoS; Pneumonia; Pseudomonas aeruginosa; Type III secretion.

Figure 1

Model of P. aeruginosa dissemination from the lung into the bloodstream. 1) Following bacterial entry into the airways, neutrophils are recruited to the alveolar space where they engage P. aeruginosa in an attempt to clear the infection. P. aeruginosa uses the type III secretion system to inject ExoS into neutrophils, which blocks phagocytosis of the bacteria and allows for bacterial persistence. 2) P. aeruginosa attaches to airway epithelial cells. Injection of ExoS into type I pneumocytes leads to the creation of “FOCI” of dead and compromised cells and the disruption of the epithelial barrier. 3) P. aeruginosa uses a type II secretion system to secrete LasB, a protease that cleaves VE-cadherin and leads to the disruption of the adherens junction of vascular endothelial cells. 4) Following endothelial cell disruption, P. aeruginosa has access to the bloodstream and disseminates throughout the body.