Targeting virulence determinants is a promising approach to controlling S. aureus infections in the face of the global spread of antibiotic resistance. S. aureus-induced peritonitis often occurs in dialysis, implant and trauma patients. To develop novel prevention and treatment options for peritoneal infection, we investigated the oligopeptide sortase A inhibitor LPRDA as a non-conventional antibacterial that does not affect staphylococcal survival. Administration of LPRDA prior to S. aureus challenge reduced the bacterial load of internal organs and bacterial colonization of the abdominal cavity in animals. In addition, LPRDA inhibited α-hemolysin production in 80% of the 35 reference and clinical S. aureus strains tested. Consequent research of LPRDA interactions with cefazolin and vancomycin has demonstrated the potential for combined application of the antivirulent and antibiotic agents under study.
Keywords: S. aureus; bacterial resistance; inhibitor; sortase; virulence; α-hemolysin.