Abstract
In an era where the pipeline of new antibiotic development is drying up, the continuous rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria are genuine threats to human health. Although antimicrobial peptides (AMPs) may serve as promising leads against drug resistant bacteria, only a few AMPs are in advanced clinical trials. The limitations of AMPs, namely their low in vivo activity, toxicity, and poor bioavailability, need to be addressed. Here, we review engineering of frog derived short α-helical AMPs (aurein, temporins) and lipopolysaccharide (LPS) binding designed β-boomerang AMPs for further development. The discovery of novel cell selective AMPs from the human proprotein convertase furin is also discussed.
Highlights
Antimicrobial peptides (AMPs) protect organisms from all kingdoms of life against infections
The innate immune system of humans and other mammals serves as a first line of defense against a wide range of invading pathogens that may encompass bacteria, fungi, viruses, and parasites [1,2,3,4]
antimicrobial peptides (AMPs) are an integral component of the host defense innate immunity
Summary
Antimicrobial peptides (AMPs) protect organisms from all kingdoms of life against infections. The mode of anti-bacterial activity of AMPs differs vastly from that of antibiotics which target intracellular macromolecules [24,25] In many cases, both outer-LPS (in Gram negative) and inner bacterial membranes are permeabilized or disrupted upon binding to AMPs, leading to cell lysis. The broad-spectrum activity and high effectiveness in bacterial cell killing by AMPs would require potential destabilization of the outer components of bacterial membranes [32,33]. The broad-spectrum activity of AMPs requires the permeabilization of both the outer and inner membrane of Gram negative bacteria. Atomic-resolution structures of potent AMPs in LPS micelles have revealed plausible disruption mechanisms of the outer membrane of Gram negative bacteria [43,44,45,46,47,48,49]. We present the discovery of non-hemolytic non-cytotoxic broad spectrum AMPs from the human protease furin
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