Executive Summary : | Objective: 1. Genetic engineering of the existing strain to enhance the levels of enzymes production for intracellular tridecaptin M synthesis
2. Bulk production of tridecaptin M using fermentation process
3. Preclinical studies (i.e., PK/PD, toxicity, in vivo efficacy in different infection models)
4. Shake flask process optimization to enhance the product yield in fermentation
5. Validation of shake flask process in 5L fermenter & Process optimization in 5L fermenter Summary: Antimicrobial resistance (AMR) is one of the most serious problems and global threat. As per recent guidelines of the World Health Organization (WHO), carbapenem-resistant Gram-negative bacteria (GNB) such as Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacte rbaumannii are the critical priority pathogens. Only limited numbers of antibiotics are available to treat these infections. Unfortunately, resistance has been reported against all the antibiotics working against GNB. Colistin is an antibiotic of last resort to treat carbapenem-resistant GNB, used as last-line antibiotic to treat such infections. However, several cases are reported of colistin resistance these days. Literally, there are no options available with global community if colistin does not work. Now it has become mandatory to find out an alternative to colistin to tackle this global health hazards. In India, the problem of antimicrobial resistance is more serious due to highly populated communities and unhygienic hospital settings. Now, it is one of the major challenges for Ministry of Health to tackle the problem of AMR and it is one of the top priorities of Government of India to provide good health for all under the flagship program “Swastha Bharat” As the panacea/path-finder for GNB infections, CSIR-IMTECH has discovered novel antibiotic which can take care of colistin resistance. We have demonstrated the activity ofTridecaptinM against colistin-resistant bacteria in murine infection model, and found to be superior tocolistin. Owing to the increase of colistin resistance in hospital pathogens, alternative drugs are urgently required. Tridecaptins are attractive drug candidates to develop them against colistin and extremely drug resistant Gram negative bacteria. Since the mechanism of action is unique than clinically approved antibiotics, the chances of cross resistance are less. The present project will focus on preclinical studies and process development for large scale production of tridecaptin M using fermentation technology. |
