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Antimicrobial resistance
Molecular Microbiology ( IF 3.6 ) Pub Date : 2022-05-27 , DOI: 10.1111/mmi.14912
Alessandra da Silva Dantas 1
Affiliation  

Molecular Microbiology is happy to offer a collection of of recently published articles that address various aspects of antimicrobial resistance. The entire collection is accessible here.

Modern medicine has benefited from the use of antimicrobial drugs to treat infectious diseases caused by bacteria, fungi, parasites and viruses. However, the recurrent use of these drugs in human, animal and environmental settings have contributed to the appearance of antimicrobial resistance (AMR) across different genera. Therefore, it is not surprising that AMR has emerged as one of the biggest threats to public and environmental health in the past 20 years. On one hand we have compiled reviews that give the readers of this special issue a historical perspective into the field (Davies & Behroozian 2020) and their role in the environment (Pishchany & Kolter 2020; Baquero et al., 2020).

AMR is associated with the ability of a population (mother cells and its progeny) to survive in the presence of these antimicrobial agents. Mechanisms of AMR seem to be conserved from prokaryotes to eukaryotes and are normally associated with processes that limit the uptake or inactivate an antimicrobial drug, modify the drug target or that actively pump the drug out of the cell. Cells can therefore survive in the presence of antimicrobial drugs by reducing permeability of the outer membrane and the activity of porins and by using/increasing multidrug-efflux pumps. Examples of resistance by modulation of porins/efflux pumps are seen in the Gram-negative bacteria Stenotrophomonas maltophilia (Calvopiña et al., 2020), Acinetobacter baumannii (Leus et al., 2020), Pseudomonas aeruginosa (Piselli & Benz 2021) and the fungal pathogen Candida lusitanie (Biermann et al., 2021). Acquisition of antibiotic resistance genes from other organisms' plasmids and conjugative transposons is also linked to AMR. More on the mobile elements and possible recombination mechanisms associated with A. baumannii AMR mechanisms can be read in this issue (Balalovski & Grainge 2020).

To survive in the presence of antimicrobial drugs bacteria, fungi and parasites need to be able to sense and respond to their environment. Hence, identifying how these signalling pathways coordinate an effective response against the deleterious effects of antibiotics might provide clues towards the development of novel antimicrobial strategies. Activation of BceS histidine kinases in the Gram-positive Bacillus subtilis, for example, signals to ensure that resistance transporters are produced in a drug dose-dependent manner with minimum energy costs (Koh et al., 2021). Furthermore, Ca2+ signalling seems to be key in mediating Neurospora crassa resistance to the antifungal peptide PAF26 (Alexander et al., 2020). The understanding of such mechanisms provides the opportunity to identify putative inhibitors either against sensor kinases such as histidine kinases in B. subtilillis or Ca2+ transporters in fungi to abrogate AMR in these organisms.

Hence, there is a need for the development of specific antimicrobial compounds that will affect microbes but will pose no threat to its host. In this issue, we highlight work that explores the use of novel antibiotics produced by microorganisms in the warfare against its competitors in the environment (Singh et al., 2020; Yan et al., 2020), the development of programmable RNA antibiotics for microbiome editing (Vogel 2020) and the use of techniques, such as cryo-EM, to aid in structure-based drug discovery and vaccine development (Shepherd et al., 2022).

From multidrug resistant bacteria to pan-resistant fungi there is a need for the development of novel antimicrobial strategies. In this special issue, we have compiled articles that mirror the efforts made by this community to understand the basis and mechanisms driving AMR in bacteria, fungi and protozoans and therefore pave the way to possible solutions against the AMR threat that has taken its toll in public health systems and environmental sectors.
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Calcofluor white stained Candida albicans yeast cells revealing budscars following antifungal treatment. Contributor: Tina Bedekovic, MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.Twitter: @tina_bedekovic, @MRCcmm



中文翻译:

抗菌素耐药性

Molecular Microbiology很高兴提供一系列最近发表的文章,这些文章涉及抗菌素耐药性的各个方面。整个系列可在此处访问。

现代医学受益于使用抗菌药物治疗由细菌、真菌、寄生虫和病毒引起的传染病。然而,这些药物在人类、动物和环境环境中的反复使用导致不同属的抗菌素耐药性 (AMR) 的出现。因此,AMR 成为过去 20 年来对公众和环境健康的最大威胁之一也就不足为奇了。一方面,我们编制了评论,让本期特刊的读者从历史角度了解该领域(Davies & Behroozian 2020)及其在环境中的作用(Pishchany & Kolter 2020;Baquero 等人,2020)。

AMR 与群体(母细胞及其后代)在这些抗微生物剂存在下的生存能力有关。AMR 的机制似乎从原核生物到真核生物都是保守的,并且通常与限制摄取或灭活抗菌药物、修饰药物靶标或主动将药物泵出细胞的过程有关。因此,通过降低外膜的渗透性和孔蛋白的活性以及通过使用/增加多药外排泵,细胞可以在存在抗菌药物的情况下存活。在革兰氏阴性菌嗜麦芽窄食单胞菌(Calvopiña et al., 2020 )、鲍曼不动杆菌(Leus et al.,2020 )、铜绿假单胞菌(Piselli & Benz 2021 ) 和真菌病原体Candida lusitanie (Biermann et al., 2021 )。从其他生物的质粒和接合转座子中获取抗生素抗性基因也与 AMR 相关。有关与鲍曼不动杆菌AMR 机制相关的移动元素和可能的重组机制的更多信息,请参阅本期(Balalovski & Grainge 2020)。

为了在存在抗菌药物的情况下生存,细菌、真菌和寄生虫需要能够感知和响应它们的环境。因此,确定这些信号通路如何协调对抗生素有害影响的有效反应可能为开发新的抗菌策略提供线索。例如,在革兰氏阳性枯草芽孢杆菌中激活 BceS 组氨酸激酶发出信号,以确保以药物剂量依赖性方式以最低的能量成本产生抗性转运蛋白(Koh 等人,2021 年)。此外,Ca 2+信号传导似乎是介导粗糙脉孢菌对抗真菌肽 PAF26 抗性的关键(Alexander 等人,2020)。对这些机制的了解提供了识别推定抑制剂的机会,这些抑制剂可以针对传感器激酶(例如枯草芽孢杆菌中的组氨酸激酶)或真菌中的 Ca 2+转运蛋白,以消除这些生物体中的 AMR。

因此,需要开发能影响微生物但不会对其宿主构成威胁的特定抗微生物化合物。在本期中,我们重点介绍了探索微生物产生的新型抗生素在与环境中的竞争对手的战争中使用的工作(Singh 等人,2020 年;Yan 等人,2020 年),用于微生物组的可编程 RNA 抗生素的开发编辑(Vogel 2020 年)和使用冷冻电镜等技术来帮助基于结构的药物发现和疫苗开发(Shepherd 等人,2022 年)。

从多重耐药细菌到泛耐药真菌,需要开发新的抗菌策略。在本期特刊中,我们汇编了一些文章,这些文章反映了该社区为了解推动细菌、真菌和原生动物 AMR 的基础和机制所做的努力,从而为解决 AMR 威胁的可能解决方案铺平了道路。卫生系统和环境部门。
图片

Calcofluor 白色念珠菌白色念珠菌酵母细胞在抗真菌治疗后显示出芽痕。贡献者:英国埃克塞特埃克塞特大学 MRC 医学真菌学中心 Tina Bedekovic。Twitter:@tina_bedekovic,@MRCcmm

更新日期:2022-05-28
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