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FabG4及其抑制剂的研究进展

Advance in Research on FabG4 and Its Inhibitor.

作者信息

Dutta Debajyoti

机构信息

Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

出版信息

Front Microbiol. 2018 Jun 6;9:1184. doi: 10.3389/fmicb.2018.01184. eCollection 2018.

DOI:10.3389/fmicb.2018.01184
PMID:29946302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6008564/
Abstract

Increasing evidence from recent reports of drug-resistant mycobacterial strains poses a challenge worldwide. Drug-resistant strains often undergo mutations, adopt alternative pathways, and express drug efflux pumps to reduce or eliminate drug doses. Besides these intrinsic resistance mechanisms, bacteria can evade drug doses by forming biofilms. Biofilms are the concerted growth of adherent microorganisms, which can also be formed at the air-water interface. The growth is supported by the extracellular polymer matrix which is self-produced by the microorganisms. Reduced metabolic activity in a nutrient-deficient environment in the biofilm may cause the microorganisms to take alternative pathways that can make the microorganisms recalcitrant to the drug doses. Recent works have shown that expresses several proteins during its growth in biofilm, those when deleted, did not show any effect on mycobacterial growth in normal nutrient-sufficient conditions. Studying these unconventional proteins in mycobacterial biofilms is therefore of utmost importance. In this article, I will discuss one such mycobacterial biofilm-related protein FabG4 that is recently shown to be important for mycobacterial survival in the presence of antibiotic stressors and limited nutrient condition. In an attempt to find more effective FabG4 inhibitors and its importance in biofilm forming . , present knowledge about FabG4 and its known inhibitors are discussed. Based on the existing data, a putative role of FabG4 is also suggested.

摘要

近期关于耐药分枝杆菌菌株的报道提供了越来越多的证据,这在全球范围内构成了一项挑战。耐药菌株常常发生突变、采用替代途径并表达药物外排泵,以减少或消除药物剂量。除了这些内在的耐药机制外,细菌还可通过形成生物膜来躲避药物剂量。生物膜是附着微生物的协同生长,其也可在气-水界面形成。这种生长由微生物自身产生的细胞外聚合物基质所支持。生物膜中营养缺乏环境下代谢活性的降低可能导致微生物采取替代途径,从而使微生物对药物剂量具有抗性。近期的研究表明,[此处原文似乎缺失了某个主体]在生物膜生长过程中表达几种蛋白质,这些蛋白质在缺失时,在正常营养充足的条件下对分枝杆菌生长没有任何影响。因此,研究分枝杆菌生物膜中的这些非常规蛋白质至关重要。在本文中,我将讨论一种这样的与分枝杆菌生物膜相关的蛋白质FabG4,最近它被证明在存在抗生素应激源和营养条件有限的情况下对分枝杆菌的存活很重要。为了寻找更有效的FabG4抑制剂及其在生物膜形成中的重要性,本文讨论了关于FabG4及其已知抑制剂的现有知识。基于现有数据,还提出了FabG4的一个假定作用。

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