Synthesis and evaluation of the antibacterial and antibiofilm activity of the xenopsin peptide and its derivatives against pulmonary bacteria in vitro and in vivo.

• Grant number: 25/27766-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2026
• End date: August 31, 2029
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fernando Rogério Pavan
• Grantee: Fernando Rogério Pavan
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• City of the host institution: Araraquara
• Associated researchers: Andréia Bagliotti Meneguin ; Eduardo Festozo Vicente

Abstract

Pulmonary infections caused by resistant pathogens, such as Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and others, represent a growing public health challenge, mainly due to biofilm formation that hinders conventional antibiotic treatment. Antimicrobial peptides (AMPs) have emerged as a promising alternative due to their ability to directly target bacterial membranes and combat biofilms. Xenopsin, isolated from the skin of Xenopus laevis, has shown antimicrobial potential in preliminary studies. This project aims to expand the therapeutic potential of xenopsin using in silico approaches (machine learning and molecular docking), as well as in vitro and in vivo assays, to identify and optimize analogs with enhanced efficacy against pulmonary bacteria and biofilms. Its properties will be assessed through methodologies such as minimum inhibitory concentration, bacterial killing kinetics, and microscopy, along with tests for stability under physiological conditions (salts, variable pH, and human serum) and toxicity evaluation. Furthermore, the mechanisms of action of the peptides will be investigated, including their interaction with bacterial membranes and intracellular targets. This study aims to contribute to combating bacterial resistance and biofilm persistence in pulmonary infections, providing new therapeutic strategies based on optimized antimicrobial peptides. (AU)