Evaluation of truncation and conjugation of analogs of the hybrid peptide "IP-1" and in vitro tests against resistant strains of Mycobacterium tuberculosis.

• Grant number: 24/22925-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Janaína Teixeira Costa de Pontes
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide related to a curable infectious disease. Due to the long treatment, it is common for there to be abandonment or incorrect use of medications, allowing the emergence of bacterial resistance, with cases of strains resistant to all drugs davailable for testing already reported. Bacterial resistance is an emergency public health problem worldwide and therefore it is necessary to search for new treatment strategies. In view of this, antimicrobial peptides (AMPs) appear as a promising alternative for the treatment of infections by resistant microorganisms, since they have different mechanisms of action in relation to conventional antibiotics in addition to being less susceptible to the development of resistance. The antimicrobial peptide Iztli Peptide1 (IP-1) has interesting activity against MTB, through its mechanism of induction of cellular autophagy. Despite their promise, AMPs have limitations for clinical application, as they have high production costs and are unstable in biological environments (susceptible to degradation by proteases). Therefore, this study aims to perform structural modifications in AMP IP-1 to reduce its degradability and increase its antimicrobial activity against MTB, using structural modification strategies.