SLPW: A Virulent Bacteriophage Targeting Methicillin-Resistant Staphylococcus aureus In vitro and In vivo

Abstract

Staphylococcus aureus (S. aureus) is a Gram-positive pathogen causing a variety of infections in humans and animals. Extensive use of antibiotics has led to the emergence of methicillin-resistant S. aureus (MRSA). As an alternative antibacterial agent against drug-resistant S. aureus, a lytic phage, designated SLPW, was isolated from fecal sewage in a pig farm. The SLPW was morphologically classified under Podoviridae and contains a double-stranded DNA genome. The genome of SLPW was 17,861 bp (29.35% G+C) containing 20 open reading frames and lacked regions encoding lysogeny-related integrase gene and cI repressor gene. Phage SLPW showed a broad host range and high efficiency of plating against various types of S. aureus. One-step growth curve showed a short latency period (10 min) and a long lytic period (120 min). Phage SLPW remained stable under a wide range of temperatures or pH and was almost unaffected in chloroform or ultraviolet light. Further, it efficiently lysed MRSA strains in vitro and in vivo. Intraperitoneal phage administration at 1 h post-infection cured the mice and reduced the bacterial expression of inflammatory cytokines in mice. Specifically, the phage SLPW displayed a wide antibacterial spectrum. It was therapeutically effective against intra-abdominal infection in mice harboring different multilocus sequence typing (MLST) types of S. aureus strains. Therefore, phage SLPW is a potential therapeutic agent against MRSA infections.

Bacteriophages inhibit biofilms formed by multi-drug resistant bacteria isolated from septic wounds

“…Results from this study show that the isolated phages were thermally active even at 40°C, 50°C, and 60°C and phages remaining viable up to 60°C after 90 min of incubation. The maximum infectivity was observed at 37°C, and the least infectivity was found at 60°C (Kęsik-Szeloch et al, 2013; Piracha et al, 2014; Wang et al, 2016).…”

Phages and Immunomodulation

“…Moreover, the release of filamentous Pf Pseudomonas phage was also associated with reduced lung injury and lower cytokine levels [39]. Wang et al demonstrated that phage therapy of uninfected mice does not alter the cytokine levels and significantly lowers those levels during therapy in infected mice, attenuating inflammation caused by S. aureus [40]. Similar findings were reported by Pabary et al, whose data indicate that phage administration reduced inflammation in a murine model of lung infection, lowering inflammatory cytokine and neutrophils levels in bronchoalveolar lavage fluid [41].…”

A Phage Lysin Fused to a Cell-Penetrating Peptide Kills Intracellular Methicillin-Resistant Staphylococcus aureus in Keratinocytes and Has Potential as a Treatment for Skin Infections in Mice

“…As a potential alternative or complement to current antimicrobial agents (i.e., antibiotics), phage therapy has been drawing more and more attention as a strategy to treat MRSA infections (12,13). The potent bactericidal effect of phages is mainly attributed to their genome-encoded cell wall hydrolase, also called lysin, which exhibits a lethal effect by forming holes in the cell wall through peptidoglycan digestion (14).…”