Anti-mycobacterial peptides: made to order with delivery included.

James Carroll, Jim O' Mahony
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引用次数: 7

Abstract

"TB is too often a death sentence. It does not have to be this way,"- Nelson Mandela. Despite the success of anti-mycobacterial drugs over the past 70 years, mycobacterial disease, particularly tuberculosis is still responsible for millions of annual deaths worldwide. Additionally, the emergence of Multidrug Resistant (MDR-TB) and Extensively Drug Resistant (XDR-TB) Tuberculosis has motivated calls by the World Health Organization (WHO) for novel drugs, vaccines and diagnostic tests. Consequently, the identification and evaluation of a range of anti-mycobacterial compounds against pathogenic mycobacterial species is of paramount importance. My colleagues and I at Cork Institute of Technology (CIT) and University College Cork (UCC) have tackled this issue through the initial optimization of the rapid, robust and inexpensive microtitre alamarBlue assay (MABA) and subsequent employment of this assay to facilitate the rapid assessment of a new wave of potential therapeutic compounds, namely bacteriocins, in particular type 1 bacteriocins known as lantibiotics. The gene encoded nature of these peptides facilitates their genetic manipulation and consequent activities as anti-microbial agents. In this regard, it may be possible to one day develop diverse populations of anti-mycobacterial bacteriocins with species specific activities. This may in turn provide more targeted therapies, resulting in less side effects, shorter treatment times and thus better patient compliance. Although current drug regimes are effective in the interim, previous lessons have taught us not to be complacent. In the words of the Intel founder Andrew Grove, 'Success breeds complacency. Complacency breeds failure. Only the paranoid survive'. Armed with knowledge of previous failures, it is the duty of the scientific community to anticipate future bacterial resistance and have an arsenal of compounds standing by in such an eventuality.

抗分枝杆菌肽:订制,包括送货。
“结核病往往等同于死刑。事情并不一定是这样的。”——纳尔逊·曼德拉。尽管抗分枝杆菌药物在过去70年中取得了成功,但分枝杆菌疾病,特别是结核病,仍然造成全世界每年数百万人死亡。此外,耐多药结核病(MDR-TB)和广泛耐药结核病(XDR-TB)的出现促使世界卫生组织(世卫组织)呼吁开发新药、疫苗和诊断测试。因此,鉴定和评价一系列抗分枝杆菌化合物对致病性分枝杆菌物种是至关重要的。我和科克理工学院(CIT)和科克大学学院(UCC)的同事们通过对快速、稳健、廉价的微滴alamarBlue测定法(MABA)的初步优化,以及随后使用该测定法来促进新一波潜在治疗化合物的快速评估,即细菌素,特别是被称为lantibiotic的1型细菌素,解决了这个问题。这些肽的基因编码性质有利于它们的基因操作和随后的抗微生物活性。在这方面,有可能有一天开发出具有物种特异性活性的多种抗分枝杆菌细菌素。这可能反过来提供更有针对性的治疗,从而减少副作用,缩短治疗时间,从而提高患者的依从性。虽然目前的药物制度在过渡时期是有效的,但过去的教训告诉我们不要自满。用英特尔创始人安德鲁·格罗夫(Andrew Grove)的话来说,“成功滋生自满。”自满滋生失败。只有偏执狂才能生存。”有了以往失败的经验,科学界有责任预测未来的细菌耐药性,并为这种可能发生的情况准备一套化合物库。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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