Ω76: A designed antimicrobial peptide to combat carbapenem- and tigecycline-resistant
| Autor: | Deepesh, Nagarajan, Natasha, Roy, Omkar, Kulkarni, Neha, Nanajkar, Akshay, Datey, Sathyabaarathi, Ravichandran, Chandrani, Thakur, Sandeep, T, Indumathi V, Aprameya, Siddhartha P, Sarma, Dipshikha, Chakravortty, Nagasuma, Chandra |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Acinetobacter baumannii
Mice Inbred BALB C Time Factors Cell Membrane SciAdv r-articles Microbial Sensitivity Tests Tigecycline Protein Structure Secondary Disease Models Animal Kinetics Carbapenems Drug Design Drug Resistance Multiple Bacterial Animals Humans Health and Medicine Peritoneum Research Articles Acinetobacter Infections Antimicrobial Cationic Peptides HeLa Cells Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Ω76 is a promising drug with remarkably low toxicity, which may be used in the future for treating highly resistant infections. 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 (Ω76) displayed high efficacy against carbapenem and tigecycline-resistant Acinetobacter baumannii in mice. Mice treated with repeated sublethal doses of Ω76 displayed no signs of chronic toxicity. Sublethal Ω76 doses co-administered alongside sublethal colistin doses displayed no additive toxicity. These results indicate that Ω76 can potentially supplement or replace colistin, especially where nephrotoxicity is a concern. To our knowledge, no other existing antibiotics occupy this clinical niche. Mechanistically, Ω76 adopts an α-helical structure in membranes, causing rapid membrane disruption, leakage, and bacterial death. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|