Bacteriophage therapy for drug-resistant Staphylococcus aureus infections

Abstract

Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites in patients. This includes Staphylococcus aureus bacteremia (SaB), which exhibits a severe infection frequently associated with significant mortality rate of approximately 25%. In the absence of better alternative therapies, antibiotics is still the main approach for treating infections. However, excessive use of antibiotics has, in turn, led to an increase in antimicrobial resistance. Hence, it is imperative that new strategies are developed to control drug-resistant S. aureus infections. Bacteriophages are viruses with the ability to infect bacteria. Bacteriophages, were used to treat bacterial infections before the advent of antibiotics, but were subsequently replaced by antibiotics due to limited theoretical understanding and inefficient preparation processes at the time. Recently, phages have attracted the attention of many researchers again because of the serious problem of antibiotic resistance. This article provides a comprehensive overview of phage biology, animal models, diverse clinical case treatments, and clinical trials in the context of drug-resistant S. aureus phage therapy. It also assesses the strengths and limitations of phage therapy and outlines the future prospects and research directions. This review is expected to offer valuable insights for researchers engaged in phage-based treatments for drug-resistant S. aureus infections.

Keywords: antimicrobial resistance; bacteriophage therapy; bacteriophages; drug-resistant Staphylococcus aureus; infection.

Figure 1

Illustration of the bacteriophage lifecycle and mechanism of bacterial lysis. (A) Lytic cycle, ①Recognition of host by phage; ②Absorption of bacteriophage to bacteria; ③Phage penetrates nucleic acid; ④Replication of phage nucleic acid; ⑤Synthesis of phage elements; ⑥Assembly of progeny phages; ⑦Bacterial lysis and release of progeny phages. (B) Role of phage endolysin in bacterial lysis: in the early stage of phage infection, the phage creates holes in the bacterial cell wall with the assistance of the VAPGH protein (which degrades a part of peptidoglycan) and injects nucleic acid into the host bacteria. Phage endolysins and holin are synthesized during the late stage of progeny phage reproduction. Holin forms pores in the bacterial inner membrane, allowing endolysins to reach the peptidoglycan.