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

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.