Defensins are a family of
cationic antimicrobial peptides active against a broad range of infectious microbes including bacteria, viruses and fungi, playing important roles as innate effectors and immune modulators in immunological control of microbial
infection. Their antibacterial properties and unique mechanisms of action have garnered considerable interest in developing
defensins into a novel class of natural
antibiotic peptides to fend off pathogenic
infection by bacteria, particularly those resistant to conventional
antibiotics. However, serious pharmacological and technical obstacles, some of which are unique to
defensins and others are common to
peptide drugs in general, have hindered the development and clinical translation of
defensins as anti-infective
therapeutics. To overcome them, several technologies have been developed, aiming for improved functionality, prolonged circulation time, enhanced proteolytic stability and bioavailability, and efficient and controlled delivery and release of
defensins to the site of
infection. Additional challenges include the alleviation of potential toxicity of
defensins and their cost-effective manufacturing. In this review, we briefly introduce
defensin biology, focus on various transforming strategies and practical techniques developed for
defensins and their derivatives as antibacterial
therapeutics, and conclude with a summation of future challenges and possible solutions.