Novel Therapies for Pseudomonas aeruginosa Pneumonia

Damien      Roux; Jean-Damien      Ricard

Abstract

P. aeruginosa is the bacteria most commonly responsible for hospital-acquired and ventilator-associated pneumonia. Numerous factors are encoded in its genome, and they explain its high virulence. P. aeruginosa also develops a quorum sensing (QS), which coordinates the expression of these factors. The type III secretion system, a needle-complex, allows exotoxin injections into eukaryotic cells and is involved in the pathogenesis of acute pneumonia. This pathogen develops a high level of resistance to all antibiotics, which leads to a shortage of treatment options for many patients. Thus, new preventive or therapeutic approaches are in development. Immunotherapy that uses monoclonal antibodies has been successfully tested in blocking the type III secretion system (anti-PcrV) or helping immune cells phagocytose P. aeruginosa. Inhibiting the quorum sensing has also been efficacious in vitro and in vivo. New antibacterial peptides may enlarge the panel of treatments in the near future. However, current treatment for patients still relies on antibiotics. The development of resistance to all classes of available antibiotics leads to colistin revival with good clinical results. Topical delivery through aerosol could allow for the increase in the antibiotic concentration inside the infection site while limiting its systemic toxicity. Finally, Candida airway colonization has been found to be associated with P. aeruginosa-associated pneumonia in ventilated patients. In addition to targeting the bacteria, reducing Candida airway colonization may also decrease the incidence of such infections.

Keywords: Nosocomial infection, ventilator-associated pneumonia, immunotherapy, type III secretion system, quorum sensing (QS), acute pneumonia, eukaryotic cells, immune cells phagocytose P. aeruginosa, ubiquitous aerobic, bacterial targets, cystic fibrosi, ventilated patients, lipopolysaccharide O side chains, bronchoalveolar lavage quantitative culture, virulence factors