Csir-Institute Of Microbial Technology(Csir-Imtech), Chandigarh, Chandigarh
hemraj@imtech.res.in
CO-Principal Investigator
Nil
Project Overview
Antimicrobial resistance (AMR) is a global menace leading to the loss of 7,00,000 lives globally every year. This number is expected to grow to 10 million and cost trillions by 2050. WHO has included Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus species, and Salmonella species in the high Priority Pathogen list. The discovery pipeline of new antimicrobial has been almost dried up and there are very few additions of new antibiotic after golden period of antibiotic discovery. Resistance development has been reported against almost all antibiotics. Considering the global health hazards of AMR, there is an urgent need of new and effective antibiotic which would improve patient outcomes, reduce the risk of complications, and help to control the spread of the infection. Our group has recently isolated a broad-spectrum antibiotic compound (A32C2) from Paenibacillus dendritiformis which is active against gram-positive and gram-negative bacteria. We have elucidated the structure of the compound, which confirms its novelty (not disclosed here due to IP issue). The compound has a MIC in the range of 0.5-4 µg/ml against various MDR isolates of S. aureus and K. pneumoniae. No significant hemolysis was observed up to 500 µg/ml. The results of cytotoxicity experiments in human embryonic kidney cell line HEK293 and Human monocytic cell line THP1 demonstrate IC50 of ~500 µg/ml. We have also evaluated the efficacy of A32C2in mice skin infection model, and showed better efficacy than Mupirocin. These results indicate that A32C2 is a promising agent for tackling ESKAPE infections and thus our objective will be to elucidate the mechanism of action, to evaluate the spectrum of antibiotic on clinical isolates, in vivo safety and efficacy in mice models and efficient formulation development to treat infections. Since it is novel antibiotic, we may land into novel insight of mechanism of action which will have significant impact in the area of AMR. Due to its novelty, the chances of possible cross resistance or immediate resistance to this antibiotic will be less. The fundamental findings in the proposed project will lead to the proof of concept (POC) for pre-clinical and clinical studies of this novel antibiotic for future application.