Banca de QUALIFICAÇÃO: RAFAEL BARBOSA DE MOURA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : RAFAEL BARBOSA DE MOURA
DATE: 05/02/2025
TIME: 14:00
LOCAL: Google meet
TITLE:

Evaluation of Molecular Docking and Modulatory Antibacterial Activity of Lectins from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) Against Bacterial Strains with NorA and MepA Efflux Pumps

 

 

 

 

KEY WORDS:

lectins; efflux pump; bacterial resistance; antimicrobials; molecular docking.

PAGES: 80
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Lectins are proteins capable of binding reversibly and specifically to carbohydrates. They have the ability to agglutinate erythrocytes and are found in various organisms, such as plants and prokaryotes. Plant lectins are a group of proteins with great biological potential and represent the class of lectins most widely presented in the literature. The research presented in this thesis deals with the evaluation of molecular docking and modulatory antibacterial activity of lectins from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) against bacterial strains carrying NorA efflux pumps. Lectins are proteins that bind specifically to carbohydrates and have the ability to agglutinate cells, and are found in various organisms. Plant lectins, in particular, have shown great biological potential and are widely studied in the literature. The study is justified by the growing need for new molecules that can combat bacterial resistance, a critical problem today due to the increase in antibiotic resistance mechanisms. Efflux pumps, such as NorA in Staphylococcus aureus, are mechanisms that bacteria use to expel antimicrobials, reducing the effectiveness of conventional treatments. In this study, the seeds of C. ensiformis and C. brasiliensis were crushed and extracted using 0.15M NaCl. The proteins were then purified using Sephadex-G50 gel chromatography, eluted with 0.1M glycine pH 2.6 and read in a spectrophotometer at 280 nm. After dialysis and freeze-drying, the lectins were subjected to microbiological tests. The Minimum Inhibitory Concentration (MIC) was determined for strains of S. aureus and Escherichia coli. Modulatory activity was assessed using the antibiotics gentamicin, ciprofloxacin and ampicillin. Tests were also carried out to verify the activity of the lectins against S. aureus strains carrying NorA efflux pumps. The results showed that the ConA and ConBr lectins had MICs of more than 1024 µg/mL for all the bacteria tested, and did not show significant antimicrobial activity. However, in the presence of gentamicin, ConA modulated the activity of this antibiotic in wild S. aureus strains (1199), while ConBr showed significant modulatory activity towards gentamicin and ciprofloxacin in S. aureus (1199). ConA also showed significant activity against bacteria with the NorA efflux pump in the presence of norfloxacin. In the molecular docking study, the crystallographic structures of the proteins ConA (PDB: 3enr) and ConBr (PDB: 1azd) were used as models. The ligands were prepared and submitted to the DockThor program for the docking experiments. DockThor, developed by the Molecular Modeling in Biological Systems Group at LNCC, uses a multiple solution genetic algorithm and the MMFF94S scoring function to predict poses and binding affinities. The docking results revealed that the modulating ligands exhibited stable binding conformations and favorable interaction energies with the NorA efflux pump, corroborating the experimental data on modulatory activity. It is concluded that, despite not showing relevant direct antimicrobial activity, the lectins ConA and ConBr can modulate the efficacy of antibiotics in multidrug-resistant bacterial strains, especially those with efflux pumps, offering a potential way to combat antimicrobial resistance.

COMMITTEE MEMBERS:
Externa à Instituição - CRISTINA RODRIGUES DOS SANTOS BARBOSA - URCA
Presidente - FRANCISCO NASCIMENTO PEREIRA JUNIOR
Externa à Instituição - JANAÍNA ESMERALDO ROCHA - UECE
Interno - JORGE ANDRE MATIAS MARTINS