1. Human defensin-inspired discovery of peptidomimetic antibiotics
Gan Luo, Jue Zhang, HanBin Wang, YaQi Sun, BaoLi Cheng, ZhiPeng Xu, Yan Zhang, Hui Li, WuYuan Lu, Elizabeta Nemeth, Tomas Ganz, XiangMing Fang Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2117283119. doi: 10.1073/pnas.2117283119. Epub 2022 Mar 1.
SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.
2. Defensin-based anti-infective strategies
Miriam Wilmes, Hans-Georg Sahl Int J Med Microbiol. 2014 Jan;304(1):93-9. doi: 10.1016/j.ijmm.2013.08.007. Epub 2013 Sep 4.
Cationic and amphiphilic peptides are widely distributed in eukaryotic organisms and constitute a first line of host defense against invading pathogens. Some of these host defense peptides (HDPs) combine specific antibiotic activities with modulation of immune responses. Moreover, they are active against bacteria resistant to conventional antibiotics and show only modest resistance development under in vitro selection pressure. Based on these features, HDPs and particularly defensins are considered a promising source of novel anti-infective agents. This review summarizes the current knowledge about defensins from different kingdoms and discusses their potential for therapeutic application.
3. Defensin-lipid interactions in membrane targeting: mechanisms of action and opportunities for the development of antimicrobial and anticancer therapeutics
Matthew J A Hein, Marc Kvansakul, Fung T Lay, Thanh Kha Phan, Mark D Hulett Biochem Soc Trans. 2022 Feb 28;50(1):423-437. doi: 10.1042/BST20200884.
Defensins are a class of host defence peptides (HDPs) that often harbour antimicrobial and anticancer activities, making them attractive candidates as novel therapeutics. In comparison with current antimicrobial and cancer treatments, defensins uniquely target specific membrane lipids via mechanisms distinct from other HDPs. Therefore, defensins could be potentially developed as therapeutics with increased selectivity and reduced susceptibility to the resistance mechanisms of tumour cells and infectious pathogens. In this review, we highlight recent advances in defensin research with a particular focus on membrane lipid-targeting in cancer and infection settings. In doing so, we discuss strategies to harness lipid-binding defensins for anticancer and anti-infective therapies.
