Antimicrobial Peptides as Potential Anti-Tubercular Leads: A Concise Review

Abstract

Despite being considered a public health emergency for the last 25 years, tuberculosis (TB) is still one of the deadliest infectious diseases, responsible for over a million deaths every year. The length and toxicity of available treatments and the increasing emergence of multidrug-resistant strains of Mycobacterium tuberculosis renders standard regimens increasingly inefficient and emphasizes the urgency to develop new approaches that are not only cost- and time-effective but also less toxic. Antimicrobial peptides (AMP) are small cationic and amphipathic molecules that play a vital role in the host immune system by acting as a first barrier against invading pathogens. The broad spectrum of properties that peptides possess make them one of the best possible alternatives for a new “post-antibiotic” era. In this context, research into AMP as potential anti-tubercular agents has been driven by the increasing danger revolving around the emergence of extremely-resistant strains, the innate resistance that mycobacteria possess and the low compliance of patients towards the toxic anti-TB treatments. In this review, we will focus on AMP from various sources, such as animal, non-animal and synthetic, with reported inhibitory activity towards Mycobacterium tuberculosis.

Tandem Repeat of a Short Human Chemerin-Derived Peptide and Its Nontoxic d-Lysine-Containing Enantiomer Display Broad-Spectrum Antimicrobial and Antitubercular Activities

“…Several smaller antimicrobial peptide segments have been identified from antimicrobial host defense proteins with potential antimycobacterial activity. 52,53 In order to search for new smaller, nontoxic antimicrobial peptides with antimycobacterial property, we evaluated the antitubercular effect of Chem-KVL and its most nonhemolytic/nontoxic analogue, Chem-8dK, against M. tuberculosis H37Ra, Mycobacterium bovis (both slow-growing strains), and Mycobacterium smegmatis (fast-growing strain) of mycobacteria (Figure 8a−c). We found that at 16.13 μM concentration, Chem-KVL and Chem-8dK inhibited ∼80 and 95% growth of these mycobacterial strains, respectively.…”

“Upcycling” known molecules and targets for drug-resistant TB

“…Finally, a new path to bypass resistance might not arise from small drug molecules but from RNA network regulation such as ncRNA modulation ( Gerrick et al., 2018 ) or proteinaceous inhibitors that may disrupt important protein-protein interaction ( Sala et al., 2014 ), or from antimicrobial peptides ( Oliveira et al., 2021 ).…”

Antibiotic Resistance to Mycobacterium tuberculosis and Potential Use of Natural and Biological Products as Alternative Anti-Mycobacterial Agents

“…Among non-animal AMPs, antibiotics produced by Lactococcus lactis exert anti-tubercular activity [ 145 ]. Especially, nisin A and lacticin 3147, as well as their mutated variants, are very effective against some MDR Mtb strains.…”