The macrophage-bacterium mismatch in persister formation.

IF 14 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Trends in Microbiology Pub Date : 2024-10-01 Epub Date: 2024-03-04 DOI:10.1016/j.tim.2024.02.009
Iris Dadole, Didier Blaha, Nicolas Personnic
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Abstract

Many pathogens are hard to eradicate, even in the absence of genetically detectable antimicrobial resistance mechanisms and despite proven antibiotic susceptibility. The fraction of clonal bacteria that temporarily elude effective antibiotic treatments is commonly known as 'antibiotic persisters.' Over the past decade, there has been a growing body of research highlighting the pivotal role played by the cellular host in the development of persisters. In parallel, this research has also sought to elucidate the molecular mechanisms underlying the formation of intracellular antibiotic persisters and has demonstrated a prominent role for the bacterial stress response. However, questions remain regarding the conditions leading to the formation of stress-induced persisters among a clonal population of intracellular bacteria and despite an ostensibly uniform environment. In this opinion, following a brief review of the current state of knowledge regarding intracellular antibiotic persisters, we explore the ways in which macrophage functional heterogeneity and bacterial phenotypic heterogeneity may contribute to the emergence of these persisters. We propose that the degree of mismatch between the macrophage permissiveness and the bacterial preparedness to invade and thrive intracellularly may explain the formation of stress-induced nonreplicating intracellular persisters.

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宿主形成过程中的巨噬细胞-细菌错配。
许多病原体很难根除,即使没有基因检测到的抗菌素抗药性机制,尽管抗生素的敏感性已得到证实。暂时躲过有效抗生素治疗的部分克隆细菌通常被称为 "抗生素持久菌"。在过去的十年中,越来越多的研究强调了细胞宿主在顽固菌发展过程中的关键作用。与此同时,这些研究还试图阐明细胞内抗生素宿主形成的分子机制,并证明了细菌应激反应的重要作用。然而,在表面环境一致的情况下,导致细胞内细菌克隆群体形成应激诱导的持久性有机污染物的条件仍然存在疑问。在本文中,我们简要回顾了目前有关细胞内抗生素宿主的知识,然后探讨了巨噬细胞功能异质性和细菌表型异质性可能导致宿主出现的方式。我们认为,巨噬细胞的容许度与细菌入侵细胞并在细胞内繁殖的准备度之间的不匹配程度可能是应激诱导的非复制细胞内持久菌形成的原因。
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来源期刊
Trends in Microbiology
Trends in Microbiology 生物-生化与分子生物学
CiteScore
25.30
自引率
0.60%
发文量
193
审稿时长
6-12 weeks
期刊介绍: Trends in Microbiology serves as a comprehensive, multidisciplinary forum for discussing various aspects of microbiology, spanning cell biology, immunology, genetics, evolution, virology, bacteriology, protozoology, and mycology. In the rapidly evolving field of microbiology, technological advancements, especially in genome sequencing, impact prokaryote biology from pathogens to extremophiles, influencing developments in drugs, vaccines, and industrial enzyme research.
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