Liu Yu, Feng Jiannan, Lu Qiang, Zhang Xin, Gao Yaping, Yan Jun, Mu Chunhua, Hei Yan, Lv Ming, Han Gencheng, Chen Guojiang, Jin Peng, Hu Weiguo, Shen Beifen, Yang Guang
Beijing Institute of Basic Medical Sciences, Beijing, China.
State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Sci Rep. 2015 Nov 24;5:17215. doi: 10.1038/srep17215.
Staphylococcus aureus causes a wide range of infectious diseases. Treatment of these infections has become increasingly difficult due to the widespread emergence of antibiotic-resistant strains; therefore, it is essential to explore effective alternatives to antibiotics. A secreted protein of S. aureus, known as eLtaS, is an extracellular protein released from the bacterial membrane protein, LtaS. However, the role of eLtaS in S. aureus pathogenesis remains largely unknown. Here we show eLtaS dramatically aggravates S. aureus infection by binding to C3b and then inhibiting the phagocytosis of C3b-deposited S. aureus. Furthermore, we developed a monoclonal antibody against eLtaS, MAE4, which neutralizes the activity of eLtaS and blocks staphylococcal evasion of phagocytosis. Consequently, MAE4 is capable of protecting mice from lethal S. aureus infection. Our findings reveal that targeting of eLtaS by MAE4 is a potential therapeutic strategy for the treatment of infectious diseases caused by S. aureus.
金黄色葡萄球菌可引发多种传染病。由于抗生素耐药菌株的广泛出现，这些感染的治疗变得越来越困难；因此，探索抗生素的有效替代物至关重要。金黄色葡萄球菌的一种分泌蛋白，称为eLtaS，是从细菌膜蛋白LtaS释放的细胞外蛋白。然而，eLtaS在金黄色葡萄球菌致病机制中的作用仍 largely未知。在这里，我们表明eLtaS通过与C3b结合，然后抑制C3b沉积的金黄色葡萄球菌的吞噬作用，从而显著加重金黄色葡萄球菌感染。此外，我们开发了一种针对eLtaS的单克隆抗体MAE4，它可中和eLtaS的活性并阻止葡萄球菌逃避吞噬作用。因此，MAE4能够保护小鼠免受致命的金黄色葡萄球菌感染。我们的研究结果表明，用MAE4靶向eLtaS是治疗由金黄色葡萄球菌引起的传染病的一种潜在治疗策略。
