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用于抗毒剂开发的分子靶标。

Molecular Targets in for the Development of Anti-Virulence Agents.

机构信息

Department of Biology, Indiana State University, 600 Chestnut St. S224, Terre Haute, IN 47809, USA.

出版信息

Genes (Basel). 2024 Sep 4;15(9):1166. doi: 10.3390/genes15091166.

Abstract

, commonly known as Group A Streptococcus (GAS), is a significant human pathogen responsible for a wide range of diseases, from mild pharyngitis to severe conditions such as necrotizing fasciitis and toxic shock syndrome. The increasing antibiotic resistance, especially against macrolide antibiotics, poses a challenge to the effective treatment of these infections. This paper reviews the current state and mechanisms of antibiotic resistance in . Furthermore, molecular targets for developing anti-virulence agents, which aim to attenuate virulence rather than killing it outright, are explored. This review specifically focuses on virulence regulators, proteins that coordinate the expression of multiple virulence factors in response to environmental signals, playing a crucial role in the pathogen's ability to cause disease. Key regulatory systems, such as RopB, Mga, CovRS, and the c-di-AMP signaling system, are discussed for their roles in modulating virulence gene expression. Additionally, potential molecular target sites for the development of anti-virulence agents are suggested. By concentrating on these regulatory pathways, it is proposed that anti-virulence strategies could enhance the effectiveness of existing antibiotics and reduce the selective pressure that drives the development of resistance.

摘要

化脓性链球菌,通常被称为 A 组链球菌(GAS),是一种重要的人类病原体,可导致多种疾病,从轻度咽炎到坏死性筋膜炎和中毒性休克综合征等严重疾病。越来越多的抗生素耐药性,特别是对大环内酯类抗生素的耐药性,对这些感染的有效治疗构成了挑战。本文综述了化脓性链球菌的抗生素耐药性现状和机制。此外,还探讨了开发抗毒力药物的分子靶点,这些药物旨在减弱毒力而不是直接杀死病原体。本综述特别关注毒力调节因子,这些因子是协调多种毒力因子表达的蛋白质,可根据环境信号来响应,在病原体引起疾病的能力中起着至关重要的作用。讨论了 RopB、Mga、CovRS 和 c-di-AMP 信号系统等关键调节系统在调节毒力基因表达中的作用。此外,还提出了针对抗毒力药物开发的潜在分子靶标。通过集中研究这些调节途径,可以提出抗毒力策略来提高现有抗生素的有效性,并降低导致耐药性发展的选择压力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3868/11430994/b66d4861c8fd/genes-15-01166-g001.jpg

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