Microbial-derived peptides with anti-mycobacterial potential

Area of Science:

• Microbiology
• Pharmacology
• Natural Products Chemistry

Background:

• Tuberculosis (TB) is a leading cause of death globally, exacerbated by multidrug-resistant strains.
• There is an urgent need for novel anti-TB drug discovery to combat resistant Mycobacterium tuberculosis.
• Microbial-derived peptides, specifically RiPPs and NRPs, are emerging as promising anti-mycobacterial agents.

Purpose of the Study:

• To review natural ribosomally synthesized and post-translationally modified peptides (RiPPs) and nonribosomal peptides (NRPs) with anti-mycobacterial activity.
• To identify promising peptide candidates for treating drug-resistant tuberculosis.
• To explore structure-activity relationships for optimizing anti-TB peptide efficacy.

Main Methods:

• Comprehensive literature review of microbial-derived anti-mycobacterial peptides.
• Analysis of in vitro activity spectra against non-resistant and drug-resistant mycobacteria.
• Identification of intracellular targets and chemical modification strategies for 96 RiPP and NRP families.

Main Results:

• 96 natural RiPP and NRP families exhibit broad-spectrum in vitro activity against various mycobacteria.
• Intracellular targets of 22 anti-mycobacterial peptides were identified.
• Chemical modifications of 38 families show potential for improved anti-TB properties.

Conclusions:

• Microbial RiPPs and NRPs represent a valuable resource for novel anti-TB drug development.
• Structure-activity relationship studies highlight key modifications for enhancing peptide potency against resistant TB.
• Further research into these peptides and their targets could lead to effective new treatments for tuberculosis.