Thanatin: An Emerging Host Defense Antimicrobial Peptide with Multiple Modes of Action.

Rachita Dash,Surajit Bhattacharjya

doi:10.3390/ijms22041522

Abstract

Antimicrobial peptides (AMPs) possess great potential for combating drug-resistant bacteria. Thanatin is a pathogen-inducible single-disulfide-bond-containing β-hairpin AMP which was first isolated from the insect Podisus maculiventris. The 21-residue-long thanatin displays broad-spectrum activity against both Gram-negative and Gram-positive bacteria as well as against various species of fungi. Remarkably, thanatin was found to be highly potent in inhibiting the growth of bacteria and fungi at considerably low concentrations. Although thanatin was isolated around 25 years ago, only recently has there been a pronounced interest in understanding its mode of action and activity against drug-resistant bacteria. In this review, multiple modes of action of thanatin in killing bacteria and in vivo activity, therapeutic potential are discussed. This promising AMP requires further research for the development of novel molecules for the treatment of infections caused by drug resistant pathogens.

Highlights

Antimicrobial resistance (AMR) is a growing complex global issue of serious concern
Novel antibiotics are urgently needed to treat infections caused by the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae) group of pathogens
No toxicity was observed against mouse primary neuron cells as well [28]. These results indicate that thanatin exhibits excellent in vivo efficacy against a broad range of pathogens, with a high degree of selectivity towards bacterial cell membranes over mammalian cell membranes

Summary

Introduction

Antimicrobial resistance (AMR) is a growing complex global issue of serious concern. Based on the trends of drug resistance ascent, the O’Neill report [1] estimates that unless appropriate action is taken, AMR will cause up to 10 million deaths annually by the year 2050. Apart from being able to target an impressively large spectrum of pathogens encompassing Gram-negative bacteria, Gram-positive bacteria, fungi, and viruses; some of these peptides can exhibit immunomodulatory effects that indirectly aid in pathogen clearance [16,17,18]. Activities such as anti-infective, anti-inflammatory, wound healing, as well as anti-biofilm properties, can be inherent to some AMPs [19]. Despite the tremendous potential of AMPs to serve as an alternative to conventional antibiotics and relieve to a degree the growing problem of antibiotic resistance, no peptide-based antibiotic has been given regulatory approval so far [19]. The lack of success in clinical translation of this class of molecules can be largely attributed to their poor stability, toxicity to the host, and high production costs [23]

Thanatin

Atomic-Resolution Structure of Thanatin in LPS Outer Membrane

Binding of Thanatin with LPS Transport Protein Complex and Interactions with

Findings

Conclusions