Antimicrobial activity of a-mangostin against <bold>Staphylococcus </bold>species from companion animals in vitro and therapeutic potential of a-mangostin in skin diseases caused by S. pseudintermedius

초록

Antimicrobial resistance in Staphylococcus species from companion animals is becoming increasingly prevalent worldwide. S. pseudintermedius is a leading cause of skin infections in companion animals. a-mangostin (a-MG) exhibits various pharmacological activities, including antimicrobial activity against G (+) bacteria. This study investigated the antimicrobial activity of a-MG against clinical isolates of Staphylococcus species from companion animals and assessed the therapeutic potential of a-MG in skin diseases induced by S. pseudintermedius in a murine model. Furthermore, the action mechanisms of a-MG against S. pseudintermedius were investigated. a-MG exhibited antimicrobial activity against clinical isolates of five different Staphylococcus species from skin diseases of companion animals in vitro, but not G (-) bacteria. a-MG specifically interacted with the major histocompatibility complex II analogous protein (MAP) domain-containing protein located in the cytoplasmic membrane of S. pseudintermedius via hydroxyl groups at C-3 and C-6. Pretreatment of S. pseudintermedius with anti-MAP domain-containing protein polyclonal serum significantly reduced the antimicrobial activity of a-MG. The sub-minimum inhibitory concentration of a-MG differentially regulated 194 genes, especially metabolic pathway and virulence determinants, in S. pseudintermedius. a-MG in pluronic lecithin organogel significantly reduced the bacterial number, partially restored the epidermal barrier, and suppressed the expression of cytokine genes associated with pro-inflammatory, Th1, Th2, and Th17 in skin lesions induced by S. pseudintermedius in a murine model. Thus, a-MG is a potential therapeutic candidate for treating skin diseases caused by Staphylococcus species in companion animals.

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