Development of a complete pathway model for the synthesis of the gram negative cell

据预测，在未来33年内，死于抗药性细菌的人数将超过死于癌症的人数。由于缺乏新的抗微生物分子的发现和开发，这一问题变得更加复杂。尤其令人担忧的是革兰氏细菌物种表现出的耐药性水平，如大肠杆菌、凯尔伯氏菌和假单胞菌。Oppilotech正在开发一个计算平台，以促进检测针对革兰氏细菌的新的抗菌靶。我们已经成功地使用这种方法来识别新的靶点，这些靶点削弱了细胞壁结构，使它们对现有药物更具渗透性。这种强化方法有能力重新激活由于高耐药性水平而不再使用的药物。它还可以减少给予抗菌剂的剂量，对已知毒性问题的药物(如粘菌素)尤其重要。最后，这种方法可能会促进使用革兰氏+Ve药物治疗革兰氏感染。如果获得资金，Oppilotech将利用这一奖项聘请一名计算生物学家来扩展现有模型，以纳入肽多聚糖的合成。这将有效地完成细菌细胞膜合成所涉及的所有主要细胞质步骤。一旦完成，这个确定的模型将与一个空间模型联系起来，目的是确定在增强活性方面最理想的药物靶点。

It is predicted that within the next 33 years, deaths attributable to antibiotic resistant bacteria will outnumber those caused by cancer. This problem is compounded by the lack of both the discovery and development of novel antimicrobial molecules. Of particular concern are the resistance levels exhibited by the Gram -ve bacterial species such as E.coli, Kelbsiella and pseudomonas. Oppilotech are developing a computational platform in order to facilitate the detection of novel antimicrobial targets against Gram-ve bacteria. We have used this method successfully to identify new targets which weaken the cell wall structures making them more permeable to existing drugs. This potentiating approach has the capacity to reactivate drugs which are no longer used because of high resistance levels. It can also reduce the doses at which antimicrobials are given, particularly important for drugs with know toxicity issues (such as colistin). Finally, this approach may facilitate the use of Gram +ve drugs for Gram -ve infections. If funded Oppilotech will use the award to employ a computational biologist to expand the existing model in order to incorporate peptidoglycan synthesis. This will effectively complete all of the main cytoplasmic steps involved in the synthesis of the bacterial cell envelope. Once complete this deterministic model will be linked with a spatial model with the aim of determining the most optimal drug target in terms of potentiating activity.