Antimicrobial Peptides and Proteins: From Nature’s Reservoir to the Laboratory and Beyond

Abstract

Rapid rise of antimicrobial resistance against conventional antimicrobials, resurgence of multidrug resistant microbes and the slowdown in the development of new classes of antimicrobials, necessitates the urgent development of alternate classes of therapeutic molecules. Antimicrobial peptides (AMPs) are small proteins present in different lifeforms in nature that provide defense against microbial infections. They have been effective components of the host defense system for a very long time. The fact that the development of resistance by the microbes against the AMPs is relatively slower or delayed compared to that against the conventional antibiotics, makes them prospective alternative therapeutics of the future. Several thousands of AMPs have been isolated from various natural sources like microorganisms, plants, insects, crustaceans, animals, humans, etc. to date. However, only a few of them have been translated commercially to the market so far. This is because of some inherent drawbacks of the naturally obtained AMPs like 1) short half-life owing to the susceptibility to protease degradation, 2) inactivity at physiological salt concentrations, 3) cytotoxicity to host cells, 4) lack of appropriate strategies for sustained and targeted delivery of the AMPs. This has led to a surge of interest in the development of synthetic AMPs which would retain or improve the antimicrobial potency along with circumventing the disadvantages of the natural analogs. The development of synthetic AMPs is inspired by natural designs and sequences and strengthened by the fusion with various synthetic elements. Generation of the synthetic designs are based on various strategies like sequence truncation, mutation, cyclization and introduction of unnatural amino acids and synthons. In this review, we have described some of the AMPs isolated from the vast repertoire of natural sources, and subsequently described the various synthetic designs that have been developed based on the templates of natural AMPs or from de novo design to make commercially viable therapeutics of the future. This review entails the journey of the AMPs from their natural sources to the laboratory.

Evidence of Antibacterial Potential of Spider Silk (Araneae: Araneidae) as Borrowed Property

“…We observed almost similar inhibition zones (20-27 mm) in both Gram positive (S. aureus) and Gram negative bacteria (E. coli and S. typhimurium 1102). This is in agreement to previous findings where authors reported that spider web possess has broad spectrum antimicrobial activity against different microorganisms, including both Gram positive and Gram negative bacteria, viruses, fungi and protozoa (Gomes et al, 2011;Sarkar et al, 2021). Wright and Goodacre (2012), compared antibacterial property of spider silk group against B. subtilis and E. coli in broth media and reported that the spider silk have bacteriostatic action on B. subtilis but no significant effect on E. coli.…”

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

“…In addition, the amino acid sequences included in the spine of amyloid fibrils are sufficiently resistant to the action of proteases, which is one of the diagnostic properties of amyloid fibrils [53,54]. This resistance can also be useful for antimicrobial peptides, allowing them to be protected from the action of exopeptidases [55]. Typically, such hybrid peptides entail reciprocal biophysical and biochemical interactions that depend on the amino acid sequence, its mobility and hydrophobicity.…”

Diverse Mechanisms of Antimicrobial Activities of Lactoferrins, Lactoferricins, and Other Lactoferrin-Derived Peptides

“…Most natural antimicrobial peptides, such as lactoferricin, are cationic in nature, containing about +2 to +9 charge in them. This highly cationic nature allows peptide to interact with LPS in outer membrane of Gram-negative bacteria [ 115 , 116 ]. It has been shown that only lactoferricin-like peptides that contain a net positive charge of at least +5 have antimicrobial activities, with the most important cationic amino acid as Arg5, as its replacement with alanine resulted in decreased antibacterial activity [ 109 , 117 ].…”

“…Many of these peptides are known to have membrane permeability and intracellular targets. It seems that tryptophan residues play a role in promoting enhanced peptide-membrane interactions [ 116 ]. The tryptophan residues are also important for the antibacterial activity of bovine lactoferricin, as a replacement of either one of the two tryptophan residues (i.e., Trp6 or Trp8) led to severe loss of antibacterial activity [ 109 , 117 ].…”