Effective Treatment of Staphylococcus aureus Intramammary Infection in a Murine Model Using the Bacteriophage Cocktail StaphLyse™

Viruses. 2023 Mar 30;15(4):887. doi: 10.3390/v15040887.

Abstract

Staphylococcus aureus causes intramammary infections (IMIs), which are refractory to antibiotic treatment and frequently result in chronic mastitis. IMIs are the leading cause of conventional antibiotic use in dairy farms. Phage therapy represents an alternative to antibiotics to help better manage mastitis in cows, reducing the global spread of resistance. A mouse mastitis model of S. aureus IMI was used to study the efficacy of a new cocktail of five lytic S. aureus-specific phages (StaphLyse™), administered either via the intramammary (IMAM) route or intravenously (IV). The StaphLyse™ phage cocktail was stable in milk for up to one day at 37 °C and up to one week at 4 °C. The phage cocktail was bactericidal in vitro against S. aureus in a dose-dependent manner. A single IMAM injection of this cocktail given 8 h after infection reduced the bacterial load in the mammary glands of lactating mice infected with S. aureus, and as expected, a two-dose regimen was more effective. Prophylactic use (4 h pre-challenge) of the phage cocktail was also effective, reducing S. aureus levels by 4 log10 CFU per gram of mammary gland. These results suggest that phage therapy may be a viable alternative to traditional antibiotics for the control of S. aureus IMIs.

Keywords: S. aureus; bacteriophage; bovine mastitis; intramammary infection; phage therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteriophages*
  • Cattle
  • Disease Models, Animal
  • Female
  • Lactation
  • Mastitis, Bovine* / drug therapy
  • Mastitis, Bovine* / microbiology
  • Mice
  • Milk / microbiology
  • Staphylococcal Infections* / microbiology
  • Staphylococcus aureus

Substances

  • Anti-Bacterial Agents

Grants and funding

Intralytix developed and manufactured StaphLyse™ and performed in vitro tests and phage characterization. The mastitis mouse model and therapy tests were funded by a research contract (no. 37574) between Université de Sherbrooke and Phileo-Lesaffre Inc. (Société Industrielle Lesaffre SA). The authors also acknowledge logistical support to J.-P.R. and F.M. laboratories from Op+lait, the Regroupement pour un lait de qualité optimale supported by the Fonds de Recherche du Québec-Nature et Technologie (FRQ-NT) (Université de Montréal, St-Hyacinthe, QC, Canada).