A review on anti‐tuberculosis peptides: Impact of peptide structure on anti‐tuberculosis activity

Abstract

Antibiotic resistance is a major public health problem globally. Particularly concerning amongst drug‐resistant human pathogens is Mycobacterium tuberculosis that causes the deadly infectious tuberculosis (TB) disease. Significant issues associated with current treatment options for drug‐resistant TB and the high rate of mortality from the disease makes the development of novel treatment options against this pathogen an urgent need. Antimicrobial peptides are part of innate immunity in all forms of life and could provide a potential solution against drug‐resistant TB. This review is a critical analysis of antimicrobial peptides that are reported to be active against the M tuberculosis complex exclusively. However, activity on non‐TB strains such as Mycobacterium avium and Mycobacterium intracellulare, whenever available, have been included at appropriate sections for these anti‐TB peptides. Natural and synthetic antimicrobial peptides of diverse sequences, along with their chemical structures, are presented, discussed, and correlated to their observed antimycobacterial activities. Critical analyses of the structure allied to the anti‐mycobacterial activity have allowed us to draw important conclusions and ideas for research and development on these promising molecules to realise their full potential. Even though the review is focussed on peptides, we have briefly summarised the structures and potency of the various small molecule drugs that are available and under development, for TB treatment.

Cathepsins and Their Endogenous Inhibitors in Host Defense During Mycobacterium tuberculosis and HIV Infection

“…Some proteins may work as antimicrobials in one context and as inhibitors of proteases in other inflammatory environments, thus compromising the antimicrobial activities of such blocked proteases. For instance, SLPI works either as antimicrobial protein and as an inhibitor which protects epithelial tissues from serine proteases including cathepsin G and neutrophil elastase while preventing their potent antimicrobial activity ( 67 , 68 ). Cathepsins B, L, and S have been shown to cleave and inactivate lactoferrin, SLPI and AMPs including defensins and cathelicidins ( Figure 1 ) ( 60 , 69 ).…”

Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

“…Several natural AMPs also demonstrated their antimicrobial activities against Mtb and, more recently, on the basis of investigated MOAs, many synthetic peptides have been designed and tested against various mycobacteria strains, providing improved and novel antimicrobial activities [20]. Several examples of both natural and chemically modified AMPs are reported in Table 1 [21]. Among the investigated models, the anti-mycobacterial compound produced by Pantoea dispersa W18 named pantocin wh-1 is a short peptide of 16 residues endowed with a cyclic structure, which demonstrated anti-Tb activity both in vitro and in vivo [22].…”

“…Furthermore, clavanin A (VFQFLGKIIHHVGNFVHGFSHVF), a 23-residue AMP that shows an α-helical conformation in a hydrophobic environment, exhibited a wide range of antimicrobial functions that are mainly exerted through liposome permeabilization and appeared enhanced upon the coordination of Zn 2+ to His 17 and His 21 [100].…”

Antibacterial activity of a new monocarbonyl analog of curcumin MAC 4 is associated with divisome disruption

“…Tuberculosis is an infectious disease caused by some mycobacteria species, especially by M. tuberculosis [32]. The first-line drugs used to treat tuberculosis patients have been the same since the 70 ′ s [33].…”