Ménage à trois – interactions between phages, bacteria and human cells in light of safety of phage therapy in staphylococcal nosocomial infections
Pneumonia caused by Staphylococcus aureus constitutes 1%–10% of cases of community-acquired pneumonia and around 20% of cases of hospital acquired pneumonia (HAP). The emergence of antibiotic resistance, especially to methicillin among nosocomial strains, resulted in difficulties in treatment, which is then responsible for prolonged hospital stays, increased mortality and morbidity of infections. The rates of methicillin resistance among clinical isolates vary from country to country, ranging from a small percent in Scandinavian countries to ~50-75% in the U.S. and Asian countries. Additionally, biofilm formation on patient’s tissues plays important role in S. aureus virulence as bacteria in biofilm are more resistant eradication. Furthermore, as individual cells detach from mature biofilm and establish new sites of infection or mediate an acute infection such as sepsis.

Bacteriophages, the viruses that infect bacteria, have been shown to be able to successfully eradicate biofilm. Phages can prevent biofilm formation and maturation by destroying bacteria in the outer layer of biofilm. They can also penetrate into biofilm matrix and break down biofilm its structure as phage lytic enzymes, depolymerase and lysins, are being released from the cells upon phage progeny release. However, in recent years a number of reports indicating that phages can interact with eukaryotic cells emerged. Therefore, there is a need to re-evaluate phage therapy in light of safety. It is important to analyse not only the cytotoxicity of phages alone but also the impact their lytic activity against bacteria may have on human cells. As progeny virions rupture the cell wall, lipoteichoic acids are released in high quantities. It has been shown that they act as inflammatory agents and their presence could lead to the worsening of the patient’s condition and negatively influencing their recovery. Additionally, genome of S. aureus is known to encode various virulence factors such as TSST-1, leucocidins and exfoliatins, that could be released rapidly and in large quantities upon cell lysis. The response of human cells to phage treatment of bacterial infections have not yet been fully analysed, but the study on cell viability and inflammatory response may provide data crucial for further development of phage therapy.