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

针对白细胞毒素 F 亚基的新型人类单克隆抗体可减少金黄色葡萄球菌引起的疾病进展和死亡率

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作者:Chendi Jing, Chenghua Liu, Fangjie Liu, Yaping Gao, Yu Liu, Zhangchun Guan, Bo Xuan, Yanyan Yu, Guang Yang

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.

Conclusions

Our findings revealed that neutralizing bicomponent leukocidins may be a promising strategy to combat infections caused by 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.

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