Evaluation of the in vitro activity of B1CTcu5 peptide analogues in macrophages infected with Mycobacterium tuberculosis.

• Grant number: 23/10440-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2023
• Effective date (End): December 29, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Laura Maria Duran Gleriani Primo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 23/16711-5 - Evaluation of the inhibitory activity of analogs of the antimicrobial peptide B1CTcu5 in portuguese clinical isolates of extensively drug-resistant Mycobacterium tuberculosis and investigation of the mechanism of action, BE.EP.IC

Abstract

Tuberculosis (TB) is an infected-contagious disease that has as principal etiological agent the bacteria Mycobacterium tuberculosis (Mtb), which is responsible for millions of deaths per year and it is the world's top infectious killer. Pulmonary macrophages phagocyte the mycobacteria to stop the infection, and may become hosts of it and may have their response modified. The pharmacological treatment (e.g. rifampicin and isoniazid) induce a bigger expression of efflux pump's genes, mechanism of resistance of Mtb. Additionally, the intracellular residence of the bacteria may invalidate the chemical therapy. However, some antimicrobial peptides (AMPs), besides their activity against membrane targets, may have inhibitory activity on efflux pumps, being alternatives for this therapeutic problem. In this way, there is the peptide B1CTcu5, from the Brevinin-1 family, that has activity against Mtb. Our research group has developed B1CTcu5 analogues (CR22-DKs16, CR22-DK18G and CR21-BR34) that demonstrated better activity and specificity of isoniazid. The objective of this project is the evaluation of the in vitro activity of B1CTcu5 peptide analogues in macrophages infected with Mtb. It aims at the qualification of a potential therapeutic strategy against resistant Mtb.