Optimization and elucidation of cationic peptides antibacterial activity in multidrug-resistant pathogens

• Grant number: 18/15887-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2018
• End date: March 31, 2022
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ilana Lopes Baratella da Cunha Camargo
• Grantee: Gabriela Marinho Righetto
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

The emergence of Multiple Drug Resistance (MDR), a consequence of the exorbitant use of antibiotics, allied with the pharmaceutical industry's lack of investment in the discovery of new drugs, has resulted in a worldwide alert due to the scarcity of therapeutic options for bacterial infections. In this scenario, interests in the search for new antimicrobial compounds increases. Given the potential of cationic peptides in this application, this project aims to explore possible optimizations for Plantaricin 149 and Bothropstoxin-I. These peptides, although characterized and active, have much higher action concentration than the therapeutic concentrations of commercial antibiotics. Therefore, this project proposes the synthesis of analogs based on these peptides, aiming to potentialize the action of these molecules, increase their selectivity and reduce their size. These analogues will also be suggested according to pharmacochemical parameters calculated by chemoinformatics techniques, attaching a new perspective in the analysis of these peptides. Thus, it is proposed that these peptides are designed, optimized and experimentally evaluated by determining the Minimum Inhibitory Concentration (MIC) and hemolysis rate. The analogue presenting the best results will proceed for studies with the purpose of elucidating the action mechanism of these molecules - such as time kill assay, microscopy techniques, membrane depolarization, among others. This project aims the learning of other techniques at the University of British Columbia, which will contribute to this elucidation. Bacteria from the ""ESKAPE"" group will be the focus of research for this MDR challenge. In conclusion, it is expected to obtain analogous sequences to the known peptides, but with better antimicrobial activities and to describe their action mechanism. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

UNAS DAZA, JORGE HUMBERTO; RIGHETTO, GABRIELA MARINHO; CHAUD, MARCO VINICIUS; AMARO MARTINS, VIRGINIA DE CONCEICAO; BARATELLA DA CUNHA CAMARGO, ILANA LOPES; DE GUZZI PLEPIS, ANA MARIA. PVA/anionic collagen membranes as drug carriers of ciprofloxacin hydrochloride with sustained antibacterial activity and potential use in the treatment of ulcerative keratitis. JOURNAL OF BIOMATERIALS APPLICATIONS, v. 35, n. 3, p. 12-pg., 2020-06-22. (18/15887-4)

UNAS DAZA, JORGE HUMBERTO; RIGHETTO, GABRIELA MARINHO; CHAUD, MARCO VINICIUS; AMARO MARTINS, VIRGINIA DE CONCEICAO; BARATELLA DA CUNHA CAMARGO, ILANA LOPES; DE GUZZI PLEPIS, ANA MARIA. PVA/anionic collagen membranes as drug carriers of ciprofloxacin hydrochloride with sustained antibacterial activity and potential use in the treatment of ulcerative keratitis. JOURNAL OF BIOMATERIALS APPLICATIONS, JUN 2020. (18/15887-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RIGHETTO, Gabriela Marinho. Optimization and elucidation of cationic peptides antibacterial activity in multidrug-resistant pathogens.. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.