通过可溶性肽聚糖片段感知和反应的细菌毒力调节:知识差距和治疗潜力。

IF 10.1 2区 生物学 Q1 MICROBIOLOGY
María Escobar-Salom, Isabel María Barceló, Elena Jordana-Lluch, Gabriel Torrens, Antonio Oliver, Carlos Juan
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引用次数: 1

摘要

鉴于抗生素耐药性现象造成的日益严重的临床流行病学威胁,迫切需要新的治疗方案,特别是针对ESKAPE组内的顶级医院病原体。在这种情况下,研究被推动探索治疗替代方案,其中,那些以减少细菌致病力为导向的研究可能会带来令人鼓舞的选择。然而,开发这些抗毒武器的第一步是找到细菌生物学中的弱点,以抑制发病机制。在这方面,在过去的几十年里,一些研究直接/间接地表明,某些可溶性肽聚糖衍生的片段显示出毒力调节能力,可能通过类似的机制来调节几种β-内酰胺酶的产生:结合特定的转录调节剂和/或感应/激活双组分系统。这些数据表明,细胞内和细胞间肽聚糖衍生的信号传导能够影响细菌的行为,因此可能从治疗的角度加以利用。以众所周知的肽聚糖代谢相关β-内酰胺酶调节现象为出发点,我们收集并整合了将可溶性肽聚糖感知与革兰氏阴性适应度/毒力调节联系起来的研究,剖析了当前知识中需要填补的空白,以实现潜在的治疗策略开发,这也是最后讨论的主题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential.

Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential.

Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential.

Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential.

Given the growing clinical-epidemiological threat posed by the phenomenon of antibiotic resistance, new therapeutic options are urgently needed, especially against top nosocomial pathogens such as those within the ESKAPE group. In this scenario, research is pushed to explore therapeutic alternatives and, among these, those oriented toward reducing bacterial pathogenic power could pose encouraging options. However, the first step in developing these antivirulence weapons is to find weak points in the bacterial biology to be attacked with the goal of dampening pathogenesis. In this regard, during the last decades some studies have directly/indirectly suggested that certain soluble peptidoglycan-derived fragments display virulence-regulatory capacities, likely through similar mechanisms to those followed to regulate the production of several β-lactamases: binding to specific transcriptional regulators and/or sensing/activation of two-component systems. These data suggest the existence of intra- and also intercellular peptidoglycan-derived signaling capable of impacting bacterial behavior, and hence likely exploitable from the therapeutic perspective. Using the well-known phenomenon of peptidoglycan metabolism-linked β-lactamase regulation as a starting point, we gather and integrate the studies connecting soluble peptidoglycan sensing with fitness/virulence regulation in Gram-negatives, dissecting the gaps in current knowledge that need filling to enable potential therapeutic strategy development, a topic which is also finally discussed.

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来源期刊
FEMS microbiology reviews
FEMS microbiology reviews 生物-微生物学
CiteScore
17.50
自引率
0.90%
发文量
45
审稿时长
6-12 weeks
期刊介绍: Title: FEMS Microbiology Reviews Journal Focus: Publishes reviews covering all aspects of microbiology not recently surveyed Reviews topics of current interest Provides comprehensive, critical, and authoritative coverage Offers new perspectives and critical, detailed discussions of significant trends May contain speculative and selective elements Aimed at both specialists and general readers Reviews should be framed within the context of general microbiology and biology Submission Criteria: Manuscripts should not be unevaluated compilations of literature Lectures delivered at symposia must review the related field to be acceptable
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