Antimicrobial peptides: new drugs for bad bugs?

Abstract

Antibiotics have been among the most successful classes of therapeutics and have enabled many of modern medicine’s greatest advances. However, antibiotic-resistant bacteria are emerging as critical public health threats, with recent accounts of bacterial strains resistant to all approved antibiotics. Antimicrobial peptides (AMPs) are naturally occurring molecules with the potential to serve as the basis for a new class of anti-infectives targeting these difficult-to-treat bacteria. The unique activities and features of AMPs are discussed, with a focus toward the clinical importance of priming the antibiotic pipeline and the role AMPs can fulfill in the future of fighting drug-resistant bacteria.

Comparative functional properties of engineered cationic antimicrobial peptides consisting exclusively of tryptophan and either lysine or arginine

“…In the last two decades, our laboratory has focused on rationally engineering AMPs to overcome intrinsic limitations of natural AMPs (Tencza et al, 1999;Phadke et al, 2002;Deslouches et al, 2005;Skinner et al, 2010Steckbeck et al, 2014. Hence, we previously reported the rational design of an optimized engineered cationic antimicrobial peptide (eCAP) series consisting exclusively of arginine and tryptophan residues (WR series) that display broad activity against a diverse spectrum of Grampositive and Gram-negative bacteria, including extensively drug-resistant (XDR) strains (Deslouches et al, 2013).…”

Highly potent antimicrobial peptide derivatives of bovine cateslytin

“…12 Given the ubiquitous nature of AMPs in mammals and other organisms, there is high potential for an optimized peptide therapeutic to treat bacterial infections and more importantly infections of multidrug-resistant bacteria. 13 However, AMPs have not yet been successful as therapeutics and require more research to enable the design of highpotential AMP drug candidates. This is partially caused by the challenge that a "membrane" as a target poses, as every cell has a membrane.…”

Designing Antimicrobial Peptide: Current Status

“…Furthermore, AMP length can affect its cytotoxicity. For instance, a shorter derivative of hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), if we compare it to the original form, is extremely less toxic to human red blood cells. Thus, when the goal is to design a low toxic AMP, the length of the sequence must be taken into consideration.…”

“…In the past years, conventional antibiotics growth has gradually deteriorated, only two novel antibiotics have been permitted for public use in the past 8 years, and the latest novel class, daptomycin, was introduced thirteen years ago 5 . Multidrug-resistant (MDR) microorganisms are progressively predominant with a death rate reaching fiftypercent 6 . An important feature of AMPs over conventional antibiotics is that widespread resistance has not been reported.…”