Abstract:
Staphylococcus aureus is a Gram-positive bacterium capable of infecting nearly all host tissues, causing severe morbidity and mortality. Widespread antimicrobial resistance has emerged among S. aureus clinical isolates, which are now the most frequent causes of nosocomial infection among drug-resistant pathogens. S. aureus produces an array of virulence factors that enhance in vivo fitness by liberating nutrients from the host or evading host immune responses. Staphylococcal virulence factors have been identified as viable therapeutic targets for treatment, as they contribute to disease pathogenesis, tissue injury, and treatment failure. Antivirulence strategies, or treatments targeting virulence without direct toxicity to the inciting pathogen, show promise as an adjunctive therapy to traditional antimicrobials. This Mini Review examines recent research on S. aureus antivirulence strategies, with an emphasis on translational studies. While many different virulence factors have been investigated as therapeutic targets, this review focuses on strategies targeting three virulence categories: pore-forming toxins, immune evasion mechanisms, and the S. aureus quorum sensing system. These major areas of S. aureus antivirulence research demonstrate broad principles that may apply to other human pathogens. Finally, challenges of antivirulence research are outlined including the potential for resistance, the need to investigate multiple infection models, and the importance of studying antivirulence in conjunction with traditional antimicrobial treatments.
摘要:
金黄色葡萄球菌是一种革兰氏阳性细菌,能够感染几乎所有的宿主组织,导致严重的发病率和死亡率。金黄色葡萄球菌临床分离株出现了广泛的抗菌药物耐药性,这是目前耐药病原体中最常见的医院感染原因。金黄色葡萄球菌产生一系列毒力因子,其通过从宿主释放营养物或逃避宿主免疫应答来增强体内适应性。葡萄球菌毒力因子已被确定为可行的治疗靶点,因为它们有助于疾病的发病机理,组织损伤,治疗失败。抗毒力策略,或针对毒力的治疗,而对煽动病原体没有直接毒性,显示作为传统抗菌药物的辅助疗法的希望。这篇迷你评论审查了金黄色葡萄球菌抗毒力策略的最新研究,重点是翻译研究。虽然已经研究了许多不同的毒力因子作为治疗靶标,这篇综述的重点是针对三种毒力类别的策略:成孔毒素,免疫逃避机制,和金黄色葡萄球菌群体感应系统。金黄色葡萄球菌抗毒力研究的这些主要领域证明了可能适用于其他人类病原体的广泛原理。最后,概述了抗毒力研究的挑战,包括潜在的抗药性,需要研究多种感染模型,以及与传统抗菌治疗结合研究抗毒力的重要性。