Efficacy Assessment of Phage Therapy in Treating Staphylococcus aureus-Induced Mastitis in Mice

Abstract

The primary aim of this study was to evaluate the efficacy of phage against mastitis induced by drug-resistant S. aureus in a mouse model. In this study, five S. aureus phages—4086-1, 4086-2, 4086-3, 4086-4, and 4086-6—were isolated from milk samples secreted by mastitis cows. Transmission electron microscopy showed that all the five phages had icosahedral heads and short non-contractile tails, which are typical characteristics of the family Podoviridae. All these phages were species-specific against S. aureus. The one-step growth curve showed a short latency period (10–20 min) and high burst size (up to 400 PFU/infected cell). To evaluate the effectiveness of the phage 4086-1 in the treatment against mastitis, a mouse model of mastitis was challenged with drug-resistant S. aureus. The results showed the proliferation of S. aureus in the mammary glands was significantly inhibited after treating by phage 4086-1. The concentrations of TNF-α and IL-6 decreased significantly, which demonstrated the phages could effectively alleviate the inflammatory responses. Furthermore, the histopathological analysis showed that inflammatory infiltration in the mammary glands was significantly reduced. These results demonstrate that phage may be a promising alternative therapy against mastitis caused by drug-resistant S. aureus.

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease

“…This ultimately significantly reduces mouse infections and associated inflammation, successfully saving mice from mortality ( 97 ). Another study evaluated the effectiveness of bacteriophage therapy in treating methicillin-resistant Staphylococcus aureus-induced mastitis in a mouse model ( 98 ).In the mastitis mouse model, treatment with bacteriophage 4086-1 markedly inhibited the proliferation of Staphylococcus aureus in the mammary gland. Concentrations of the inflammatory markers TNF-α and IL-6 were significantly reduced, indicating the effective alleviation of the inflammatory response by bacteriophages.…”

The current state of phage therapy in livestock and companion animals

“…After in vitro characterization of the five phages, the efficacy of a phage cocktail was confirmed in a mouse mastitis model inoculated with S. aureus CVCC 546. Phage cocktail therapy alleviated the immune response, as evidenced by the reduction in proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), along with histopathological analysis [ 36 ]. Given that previous experiments utilized a mouse model, the actual application of bacteriophages to bovine mastitis remains uncertain.…”

Therapeutic efficacy of bacteriophage drug Fagomast in clinical mastitis of cows

“…Дослідження фаготерапії in vivo проведені вченими (Breyne, 2017;Teng et al, 2022) також показали обнадійливі результати. Так, наприклад, дослідниками було проведено оцінку ефективності фагового коктейлю проти золотистого стафілококу на моделі мишей.…”

“…Також встановлено, що фаг 4086-1 значно зменшував кількість золотистого стафілококу в молочній залозі. Даний факт підтверджений результатами патологічного аналізу, який продемонстрував, що бактеріофаги знизили щільність бактеріальної популяції до рівня, який може дозволити імунній системі господаря захиститися та очистити організм від інфекції (Teng et al, 2022). Також доведено, що ΦSA012 і ΦSA039 мають літичний ефект у широкому діапазоні штамів S. aureus, виділених з молока маститних корів.…”