AUTHOR=Park Seong Yong , Lee Jung Hwa , Ko Seo Yeon , Kim Nayeong , Kim Seong Yeop , Lee Je Chul 

TITLE=Antimicrobial activity of α-mangostin against Staphylococcus species from companion animals in vitro and therapeutic potential of α-mangostin in skin diseases caused by S. pseudintermedius

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1203663

DOI=10.3389/fcimb.2023.1203663

ISSN=2235-2988

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