November 2021

M Shin, C Gómez-Garzón, and SM Payne. “Vanadate inhibits Feo-mediated iron transport in Vibrio cholerae.” Metallomics, 13, 11, Pp. mfab059. Publisher's Version Abstract
Iron is an essential element for Vibrio cholerae to survive, and Feo, the major bacterial system for ferrous iron transport, is important for growth of this pathogen in low-oxygen environments. To gain insight into its biochemical mechanism, we evaluated the effects of widely used ATPase inhibitors on the ATP hydrolysis activity of the N-terminal domain of V. cholerae FeoB. Our results showed that sodium orthovanadate and sodium azide effectively inhibit the catalytic activity of the N-terminal domain of V. cholerae FeoB. Further, sodium orthovanadate was the more effective inhibitor against V. cholerae ferrous iron transport in vivo. These results contribute to a more comprehensive biochemical understanding of Feo function, and shed light on designing effective inhibitors against bacterial FeoB proteins.
M Shin, D Mun, J Choi, S Kim, S.M. Payne, and Y Kim. “Identification of a New Antimicrobial Agent against Bovine Mastitis-Causing Staphylococcus aureus.” J. Agric. Food Chem., 69, 34, Pp. 9968–9978. Publisher's Version Abstract
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.

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