by S. Marvin Friedman
The emergence of multiple drug-resistant bacterial strains, the prevalence of recalcitrant biofilm configurations, and the reluctance of the pharmaceutical industry to initiate new antibiotic discovery programs have led to the development of a formidable population of bacterial pathogens that is increasingly difficult to control. After a long but successful era of research that had all but eliminated serious threats from bacterial infections, we are now facing this dire problem once again. In response, researchers have recently been exploring alternative approaches to antibiotic therapy including identifying chemical agents that antagonize quorum sensing and thus prevent population-wide expression of virulence genes, as well as employing either intact bacteriophages or their isolated lysins to directly kill their pathogenic bacterial hosts. Lysins kill Gram-positive bacteria by hydrolyzing the peptidoglycan in the cell wall, thereby causing cell lysis. Gram-negative bacteria are immune to their action because their outer membrane does not allow the lysins access to their peptidoglycan. I will now summarize two recent papers that use intact phages to combat two important bacterial pathogens, both in vitro and in vivo.
One of the important applications for phage therapy is for treating cystic fibrosis (CF). CF is an inherited genetic disorder where a defective enzyme results in the production of unusually viscous, sticky mucus and chloride-containing secretions in ducts and body cavities. The lungs, in particular, are seriously compromised and are readily infected, typically by Pseudomonas aeruginosa. Initial colonization usually occurs during early childhood. The ensuing chronic infection eventually causes death due to respiratory failure in 80–95% of CF patients. Treatment of these patients is impeded by the multiple mechanisms of antibiotic resistance harbored by these strains of P. aeruginosa and by their ability to form biofilms in the lung.