Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, United States.
Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, United States.
Curr Drug Targets. 2018;19(2):111-127. doi: 10.2174/1389450117666161128123536.
Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease.
In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins.
The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era.
金黄色葡萄球菌是一种主要的细菌病原体，能够引起人类从胃肠道疾病、皮肤和软组织感染到败血症等严重感染。人类的葡萄球菌感染可能频繁且反复发作，由于抗生素耐药的金黄色葡萄球菌菌株的持续存在，治疗效果越来越差。由于抗生素耐药的普遍性，以及目前抗生素开发的局限性，一个积极且非常有前途的研究领域是开发专门抑制金黄色葡萄球菌产生的毒力因子活性的策略，作为治疗疾病的替代手段。
在这篇综述中，我们特别强调了金黄色葡萄球菌产生的几种主要毒力因子，最近在抗毒力方法方面的进展可能为治疗这种病原体引起的疾病提供了一种替代手段。抑制毒力因子的策略范围从小分子抑制剂到抗体，再到毒力蛋白的突变体和类毒素形式。
金黄色葡萄球菌抗生素耐药菌株的主要流行率，加上新抗生素发现的缺乏，突显了需要大力研究对抗这种高度成功病原体引起的疾病的替代策略。目前，为治疗由金黄色葡萄球菌引起的严重疾病而开发特定的抗毒力策略、疫苗方法和替代疗法的努力，有可能遏制我们在抗生素后时代面临的局限性。
