Carroll James, O' Mahony Jim
Department of Biological Sciences, Cork Institute of Technology, Rossa Avenue, Bishopstown, Cork, Ireland.
Bioeng Bugs. 2011 Sep-Oct;2(5):241-6. doi: 10.4161/bbug.2.5.16229. Epub 2011 Sep 1.
"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.
“结核病常常是死刑判决。但不必如此。”——纳尔逊·曼德拉。尽管在过去70年里抗分枝杆菌药物取得了成功，但分枝杆菌病，尤其是结核病，每年仍在全球造成数百万人死亡。此外，耐多药（MDR-TB）和广泛耐药（XDR-TB）结核病的出现促使世界卫生组织（WHO）呼吁研发新型药物、疫苗和诊断测试。因此，鉴定和评估一系列针对致病性分枝杆菌物种的抗分枝杆菌化合物至关重要。我和我在科克理工学院（CIT）及科克大学学院（UCC）的同事们通过对快速、稳健且廉价的微量滴定板alamarBlue检测法（MABA）进行初步优化，以及随后运用该检测法来快速评估一波新的潜在治疗化合物，即细菌素，特别是被称为羊毛硫抗生素的1型细菌素，解决了这个问题。这些肽的基因编码特性便于对其进行基因操作，以及作为抗菌剂的后续活性研究。在这方面，也许有一天有可能开发出具有物种特异性活性的多种抗分枝杆菌细菌素群体。这反过来可能会提供更具针对性的疗法，从而减少副作用、缩短治疗时间，进而提高患者的依从性。尽管目前的药物治疗方案在此期间是有效的，但以往的经验教训告诉我们不能自满。用英特尔创始人安德鲁·葛洛夫的话说，“成功滋生自满。自满导致失败。只有偏执狂才能生存”。鉴于对以往失败的了解，科学界有责任预测未来的细菌耐药性，并在这种情况下储备一系列化合物。
