Inactivation of Vancomycin Resistance Genes in Enterococcus spp. Using CRISPR/Cas

• Grant number: 24/03154-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Cristina Gales
• Grantee: Josiane Trevisol Leal
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

Growing antimicrobial resistance threatens public health, requiring detailed studies toguide effective interventions(Rogers et. al., 2020). With the high incidence of communicable diseasesand scarce data in low- and middle-income countries (Iskandar et.al., 2021; Styczynski et. al., 2023), Brazil lacks updated information on the genomics of blood infections caused by Enterococcus spp. This data deficit makes it difficult to develop new therapies, while existing options lose efficacy due to increased resistance (Aung et. al., 2023). Infectionsby resistant bacteria increase morbidity, mortality and healthcare costs. With few recent pharmaceutical advances and growing resistance to antimicrobialsexisting, new treatment methods are urgently needed. Gene editing with CRISPR-Cas appears as a promising alternative, although its use in bacteria is still in its early stages. There are only four published studies using CRISPR-Cas to inactivate resistance genes inEnterococcus spp.and none in Brazil, highlighting an area of great potential to be explored at a national level. Furthermore, the use of alternative in vivo models such as G. mellonella larvae is not yet widely explored. This project aims to fill critical gaps by characterizing the epidemiology of Enterococcus spp., developing a resistance gene inactivation platform and validating a new in vivo model, with the aim of providing an accurate tool to combatantimicrobial resistance