Omega 76: A designed antimicrobial peptide to combat carbapenem- and tigecycline-resistant Acinetobacter baumannii

Nagarajan, Deepesh and Roy, Natasha and Kulkarni, Omkar and Nanajkar, Neha and Datey, Akshay and Ravichandran, Sathyabaarathi and Thakur, Chandrani and Sandeep, T and Aprameya, Indumathi and Sarma, Siddhartha P and Chakravortty, Dipshikha and Chandra, Nagasuma (2019) Omega 76: A designed antimicrobial peptide to combat carbapenem- and tigecycline-resistant Acinetobacter baumannii. In: SCIENCE ADVANCES, 5 (7).

Preview	PDF sci_adv_5-7_2019.pdf - Published Version Download (4MB) | Preview
Preview	PDF aax1946_SM.pdf - Published Version Download (23MB) | Preview
	Microsoft Excel aax1946_Dataset_S1.xlsx - Published Supplemental Material Download (25kB)
	Archive (ZIP) aax1946_Dataset_S2.zip - Published Supplemental Material Download (5MB)
	Archive (ZIP) aax1946_Dataset_S3.zip - Published Supplemental Material Download (38MB)
	Archive (ZIP) aax1946_Protocol_S1.zip - Published Supplemental Material Download (45MB)
	Archive (ZIP) aax1946_Text_S1.zip - Published Supplemental Material Download (172kB)

Abstract

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.

Item Type:	Journal Article
Publication:	SCIENCE ADVANCES
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Additional Information:	copyright of this article belongs to AMER ASSOC ADVANCEMENT SCIENCE
Keywords:	INTENSIVE-CARE; NOSOCOMIAL INFECTIONS; RATIONAL DESIGN; COLISTIN; HOST; MECHANISMS; TRYPTOPHAN; MEROPENEM; MORTALITY; MELITTIN
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology Division of Chemical Sciences > NMR Research Centre (Formerly Sophisticated Instruments Facility)
Date Deposited:	19 Nov 2019 07:29
Last Modified:	19 Nov 2019 07:29
URI:	http://eprints.iisc.ac.in/id/eprint/63500

Actions (login required)

View Item