Kong Cin, Eng Su-Anne, Lim Mei-Perng, Nathan Sheila
School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia Bangi, Malaysia.
Front Microbiol. 2016 Dec 2;7:1956. doi: 10.3389/fmicb.2016.01956. eCollection 2016.
The spread of antibiotic resistance amongst bacterial pathogens has led to an urgent need for new antimicrobial compounds with novel modes of action that minimize the potential for drug resistance. To date, the development of new antimicrobial drugs is still lagging far behind the rising demand, partly owing to the absence of an effective screening platform. Over the last decade, the nematode has been incorporated as a whole animal screening platform for antimicrobials. This development is taking advantage of the vast knowledge on worm physiology and how it interacts with bacterial and fungal pathogens. In addition to allowing for selection of compounds with promising anti-microbial properties, the whole animal screening system has also permitted the discovery of novel compounds targeting infection processes that only manifest during the course of pathogen infection of the host. Another advantage of using in the search for new antimicrobials is that the worm itself is a source of potential antimicrobial effectors which constitute part of its immune defense response to thwart infections. This has led to the evaluation of effector molecules, particularly antimicrobial proteins and peptides (APPs), as candidates for further development as therapeutic agents. In this review, we provide an overview on use of the model for identification of novel anti-infectives. We highlight some highly potential lead compounds obtained from -based screens, particularly those that target bacterial virulence or host defense to eradicate infections, a mechanism distinct from the action of conventional antibiotics. We also review the prospect of using APPs as an antimicrobial strategy to treat infections.
细菌病原体中抗生素耐药性的传播导致迫切需要具有新型作用模式的新型抗菌化合物，以尽量减少耐药性的可能性。迄今为止，新型抗菌药物的开发仍远远落后于不断增长的需求，部分原因是缺乏有效的筛选平台。在过去十年中，线虫已被用作抗菌药物的全动物筛选平台。这一发展利用了关于蠕虫生理学及其与细菌和真菌病原体相互作用的大量知识。除了能够筛选出具有潜在抗菌特性的化合物外，全动物筛选系统还发现了针对仅在病原体感染宿主过程中才会出现的感染过程的新型化合物。在寻找新型抗菌药物中使用线虫的另一个优势是，线虫本身就是潜在抗菌效应分子的来源，这些分子构成了其免疫防御反应的一部分，用于抵御感染。这导致人们评估效应分子，特别是抗菌蛋白和肽（APPs），作为进一步开发为治疗剂的候选物。在这篇综述中，我们概述了使用线虫模型鉴定新型抗感染药物的情况。我们重点介绍了从基于线虫的筛选中获得的一些极具潜力的先导化合物，特别是那些针对细菌毒力或宿主防御以根除感染的化合物，这是一种不同于传统抗生素作用的机制。我们还综述了使用线虫APPs作为治疗感染的抗菌策略的前景。
