Advanced search
Start date
Betweenand

Development of beta-lactamase inhibitors of clinical interest

Abstract

Due to the emergence of bacteria resistant to current antibiotics, the development of new antibiotics remains one of the biggest challenges of modern medicine. In Gram negative bacilli, the production of ²-lactamases is the most important contributing factor for the acquisition of resistance to ²-lactam antimicrobials. Inhibitors developed for these ²-lactamases act in conjunction with ²-lactam antibiotics, however, a decrease in the efficiency of these combinatorial therapies has been observed, mainly through the action of variants and new ²-lactamases capable of degrading these compounds. The main objective of this project is the development of ²-lactamase inhibitors, identified and isolated from pathogenic strains presenting differentiated resistance phenotype, by using two main approaches: 1) From a cyclic peptide library previously prepared by a technique Based on split-integer properties, SICLOPPS (Split Intein-mediated Circular Ligation of Peptides and Proteins) with random codons, these library will be used to perform cellular assays (high-throughput screening assays for selection).This selection will be based on the loss of bacterial resistance to a given ²-lactam antibiotic from cells (colonies) where inhibition of the enzyme (²-lactamase) by a peptide clone occurs; 2) There will also be a search for new inhibitors from rational development usinf transition metal complexes. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)