Authors
Mark AT Blaskovich, Karl A Hansford, Yujing Gong, Mark S Butler, Craig Muldoon, Johnny X Huang, Soumya Ramu, Alberto B Silva, Mu Cheng, Angela M Kavanagh, Zyta Ziora, Rajaratnam Premraj, Fredrik Lindahl, Tanya A Bradford, June C Lee, Tomislav Karoli, Ruby Pelingon, David J Edwards, Maite Amado, Alysha G Elliott, Wanida Phetsang, Noor Huda Daud, Johan E Deecke, Hanna E Sidjabat, Sefetogi Ramaologa, Johannes Zuegg, Jason R Betley, Andrew PG Beevers, Richard AG Smith, Jason A Roberts, David L Paterson, Matthew A Cooper
Publication date
2018/1/2
Journal
Nature communications
Volume
9
Issue
1
Pages
22
Publisher
Nature Publishing Group UK
Description
The public health threat posed by a looming ‘post-antibiotic’ era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature’s control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes. Peptide libraries based on positively charged electrostatic effector sequences are ligated to N-terminal lipophilic membrane-insertive elements and then conjugated to vancomycin. These modified lipoglycopeptides, the ‘vancapticins’, possess enhanced membrane affinity and activity against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria, and retain activity against glycopeptide-resistant strains. Optimised antibiotics …
Scholar articles
MAT Blaskovich, KA Hansford, Y Gong, MS Butler… - Nature communications, 2018