Novel human monoclonal antibodies targeting the F subunit of leukocidins reduce disease progression and mortality caused by Staphylococcus aureus

Abstract

Abstract Background Staphylococcus aureus is a leading cause of Gram-positive bacterial infections worldwide; however, the treatment of S. aureus infection has become increasingly difficult due to the prevalence of methicillin-resistant S. aureus strains, highlighting the urgent need for the development of novel strategies. The complexity of S. aureus pathogenesis relies on virulence factors. Recent studies have demonstrated that leukocidins expressed by the majority of clinical isolates play important roles in the pathogenesis of S. aureus. Results In this study, we developed three human monoclonal antibodies against all F-components of leukocidins HlgABC, LukSF, and LukED with high affinity. These antibodies were found to be capable of blocking leukocidin-mediated cell lysis in vitro. Furthermore, the antibodies dramatically reduced disease progression and mortality after S. aureus infection in vivo. Conclusions Our findings revealed that neutralizing bicomponent leukocidins may be a promising strategy to combat infections caused by S. aureus.

Keywords

• Staphylococcus aureus
• Leukocidins
• Human monoclonal antibodies