BiocinBR: Bacteriocin research platform to combat pathogens resistant to critical priority antimicrobials in Brazil

• Grant number: 23/18292-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date until: March 01, 2024
• End date until: February 28, 2027
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Nilton Erbet Lincopan Huenuman
• Grantee: Zuleyma Johana Becerra Tellez
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

Bacteriocins are ribosomal peptides with highly diverse structures, produced by some bacterial lineages. In the search for therapeutic alternatives against multidrug resistant (MDR) pathogens, the research on bacteriocins has increased in the scientific community, recently incorporating strategies based on genomics, proteomics, and genetic engineering. The biodiversity present in non-impacted ecosystems may represent a rich and versatile source for bioprospecting these molecules. This project aims to build a research platform on bacteriocins with potential applications against antimicrobial-resistant pathogens, including international resistant bacterial clones circulating in Brazil, as well as Candida species resistant to antifungals. The strategy will be to screen bacteria isolated from the biodiversity of non-impacted brazilian ecosystems, including marine environments, mangroves, and herpetofauna of Cerrado and the Atlantic Forest, against a collection of Gram-positive and Gram-negative bacterial species with resistance mechanisms of medical importance (i.e., MRSA, VRE, CTX-M, NDM, KPC, OXA, IMP, VIM, SPM, BKC, GES), and clinically important fungi, previously characterized by whole genome sequencing. The identification of bacteriocin-producing species will be performed by MALDI-TOF for the creation of a BioBank. Next, whole genome sequencing will be performed for identification of bacteriocin biosynthetic clusters as well as their genetic context for the construction of recombinants that will be tested in alternative models such as Galleria mellonella. All this information will be incorporated into the "BiocinBR" platform, which will be publically available within the OneBR domain (www.onehealthbr.com). For bacteriocins with larger antibacterial spectrum, further biochemical, chemical, and physicochemical characterizations will be performed to identify the active molecules and their biological stability with potential clinical application will be evaluated, targeting the creation of an innovation product/process to be patented.