A novel broad-spectrum bacteriophage cocktail against methicillin-resistant Staphylococcus aureus: Isolation, characterization, and therapeutic potential in a mastitis mouse model

PLoS One. 2025 Jan 15;20(1):e0316157. doi: 10.1371/journal.pone.0316157. eCollection 2025.

Abstract

Bovine mastitis is a considerable challenge within the dairy industry, causing significant financial losses and threatening public health. The increased occurrence of methicillin-resistant Staphylococcus aureus (MRSA) has provoked difficulties in managing bovine mastitis. Bacteriophage therapy presents a novel treatment strategy to combat MRSA infections, emerging as a possible substitute for antibiotics. This study evaluated the therapeutic potency of a novel bacteriophage cocktail against MRSA mastitis. Two new bacteriophages (vB_SauR_SW21 and vB_SauR_SW25) with potent lytic activity against MRSA were isolated and characterized. The one-step growth curve displayed a rapid latent period (20-35 min) and substantial burst size (418 and 316 PFU/ cell). In silico analyses have confirmed the absence of antimicrobial resistance or virulence factor-encoding genes within their genomes. According to the results, combining these phages augmented their host range and virulence. The phage cocktail significantly reduced bacterial burden in a BALB/c mastitis model, demonstrating efficacy comparable to antibiotic treatment. Moreover, its administration led to decreased concentrations of IL-1β and TNF-α compared to the negative control group. The bacteriophage cocktail (SW21-SW25) exhibits a promising profile for therapeutic applications and may represent a novel substitute to antibiotics for managing MRSA bovine mastitis.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteriophages / physiology
  • Cattle
  • Disease Models, Animal*
  • Female
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Mastitis / microbiology
  • Mastitis / therapy
  • Mastitis / veterinary
  • Mastitis, Bovine / microbiology
  • Mastitis, Bovine / therapy
  • Methicillin-Resistant Staphylococcus aureus* / virology
  • Mice
  • Mice, Inbred BALB C*
  • Phage Therapy* / methods
  • Staphylococcal Infections* / microbiology
  • Staphylococcal Infections* / therapy
  • Staphylococcal Infections* / veterinary
  • Staphylococcus Phages / genetics
  • Staphylococcus Phages / physiology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Anti-Bacterial Agents

Grants and funding

This work was supported by a grant number 56578 from Tehran University of Medical Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.