Signaling and regulatory pathways of beta-lactamases in Chromobacterium violaceum

• Grant number: 21/01911-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2021
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: José Freire da Silva Neto
• Grantee: Luís Gustavo Laranjeiro Alves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 22/07135-8 - Mechanisms controlling the regulation of beta-lactamases in Chromobacterium violaceum, BE.EP.MS

Abstract

One of the major public health problems today is the emergence and spread of antibiotic resistance in pathogenic bacteria. Resistance to antibiotics mediated by beta-lactamases enzymes threatens the effectiveness of one of the most important classes of antibiotics, the beta-lactams. Previous studies by our group indicate that an environmental opportunistic bacterium, Chromobacterium violaceum, is intrinsically resistant to beta-lactam antibiotics owing to the inducible expression of two chromosomal beta-lactamases, AmpC and CphA. In this work, we intend to discovery the signaling pathways and transcription factors that control the expression of the ampC and cphA genes in C. violaceum. For this, spontaneous mutants resistant to antibiotics will be isolated in the presence of the beta-lactams cefoxitin and imipenem and characterized in respect to (i) their degree of resistance to these antibiotics (disk diffusion and MIC assays), (ii) the constitutively high expression of ampC and cphA (beta-galactosidase assays), (iii) the presence of mutations in genes involved in the signaling and regulatory pathway of these enzymes (specific and global gene sequencing). The results obtained in this work will reveal the profile of mutations that lead to high expression of ampC and cphA and that lead to resistance to beta-lactam antibiotics mediated by these beta-lactamases in C. violaceum. Our data can contribute to improve strategies against antibiotic resistance in bacteria.

Academic Publications

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

ALVES, Luís Gustavo Laranjeiro. Signaling and regulatory pathways of beta-lactamases in Chromobacterium violaceum. 2024. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.