Staphylococcus aureus RF122 is a major pathogen that causes
bovine mastitis, which is the most prevalent and costly disease in the milk and dairy industry. S. aureus expresses various
virulence factors that are especially highly associated with
iron metabolism, and the bacterial ferrous
iron transport system Feo is important for bacterial growth or virulence in mammalian hosts. In this study, we evaluated a new
antimicrobial agent,
PHT-427, targeting the S. aureus RF122 Feo system for the prevention of
bovine mastitis. Various analyses on in vitro enzymatic assays, growth inhibition, virulence expressions, and toxicity of animal model systems were conducted to characterize the inhibition properties of
PHT-427. This small molecule efficiently inhibited
enzyme activity of FeoB and bacterial growth.
PHT-427 attenuated various
virulence factors related to milk quality, including
staphyloxanthin production, biofilm formation, and coagulation. Considering the high frequency of
antibiotic-resistant S. aureus in
bovine mastitis isolates,
PHT-427 synergistically enhanced bacterial
antibiotic susceptibility and further inhibited global Gram-positive bacterial growth. Unlike its effects on bacteria, the inhibitor did not show any toxicity on animal model systems. These results indicate that the S. aureus Feo system represents a good target for antimicrobial strategies, and this new
antimicrobial agent may represent a promising biotechnological application for preventing S. aureus-induced
bovine mastitis in the milk and dairy industry.