Potential application of the antimicrobial peptide analogs "B1CTcu5" as an inhibitor of the efflux pumps of Mycobacterium tuberculosis.

• Grant number: 24/17918-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Yasmin Rossi
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (Mtb), a pathogen that remains one of the main global public health challenges. The resistance of Mtb to drugs such as rifampicin and isoniazid, and the emergence of resistant strains, hinder the effective treatment of the disease. In this context, one of the mechanisms of this mycobacterium's drug resistance is related to the action of bacterial efflux pumps, which decrease the concentration of drugs in the intracellular environment of Mtb, thereby reducing their predicted effectiveness. Given this scenario, microbiology has been studying antimicrobial peptides (AMPs), which are part of the immune system of their hosts and have the ability to eliminate pathogenic microorganisms. For instance, the AMP B1CTcu5 shows promising potential in inhibiting efflux pumps. Consequently, this proposed study will focus on investigating the analogs CR22-Dks18G, CR22-DKs9, and CR23DK-R of the AMP B1CTcu5, aiming to understand their activity against Mtb and elucidate their mechanism of action. The hypothesis is that these analogs inhibit the efflux pumps of Mtb, thereby increasing the treatment efficacy. In this context, to test this hypothesis, assays will be conducted on the intracellular accumulation of ethidium bromide (EtBr), gene expression analysis of efflux pumps by qPCR, REMA and an adaptation of REDCA. Thus, the results of this project may provide relevant data on the functioning of AMPs as efflux pump inhibitors and their therapeutic potential, contributing to new therapeutic approaches against TB and improving existing treatments.