Omega 76: A designed antimicrobial peptide to combat carbapenem- and tigecycline-resistant Acinetobacter baumannii
| Autor: | Neha Nanajkar, T Sandeep, Sathyabaarathi Ravichandran, Siddhartha P. Sarma, Chandrani Thakur, Akshay Datey, Deepesh Nagarajan, Dipshikha Chakravortty, Natasha Roy, Omkar Kulkarni, Nagasuma Chandra, Indumathi Vrithamani Aprameya |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Carbapenem
medicine.drug_class Antibiotics Antimicrobial peptides Tigecycline Drug resistance Molecular Biophysics Unit Biochemistry Microbiology 03 medical and health sciences polycyclic compounds medicine 030304 developmental biology Microbiology & Cell Biology 0303 health sciences Multidisciplinary biology 030306 microbiology business.industry NMR Research Centre (Formerly Sophisticated Instruments Facility) biochemical phenomena metabolism and nutrition biology.organism_classification Antimicrobial Acinetobacter baumannii Colistin business medicine.drug |
| Zdroj: | IndraStra Global. |
| ISSN: | 2381-3652 |
| Popis: | Drug resistance is a public health concern that threatens to undermine decades of medical progress. ESKAPE pathogens cause most nosocomial infections, and are frequently resistant to carbapenem antibiotics, usually leaving tigecycline and colistin as the last treatment options. However, increasing tigecycline resistance and colistin's nephrotoxicity severely restrict use of these antibiotics. We have designed antimicrobial peptides using a maximum common subgraph approach. Our best peptide (Omega 76) displayed high efficacy against carbapenem and tigecycline-resistant Acinetobacter baumannii in mice. Mice treated with repeated sublethal doses of Omega 76 displayed no signs of chronic toxicity. Sublethal Omega 76 doses co-administered alongside sublethal colistin doses displayed no additive toxicity. These results indicate that Omega 76 can potentially supplement or replace colistin, especially where nephrotoxicity is a concern. To our knowledge, no other existing antibiotics occupy this clinical niche. Mechanistically, Omega 76 adopts an a-helical structure in membranes, causing rapid membrane disruption, leakage, and bacterial death. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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