Comparative genomics and antimicrobial activity of recombinant phage endolisins against multi-resistant gram-negative bacteria

• Grant number: 20/01535-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2020
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Marcelo Brocchi
• Grantee: Marco Túlio Pardini Gontijo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Gram-negative bacteria such as Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Salmonella and Helicobacter pylori are multiresistant bacteria of clinical interest. Recombinant phage endolysins therefore appear as potential new antimicrobials to combat infections caused by antibiotic-resistant Gram-negative bacteria. Endolysins target the peptidoglycan layer, highly conserved structure that maintains the integrity of bacterial cells. Studies show that the main barrier to exogenous application of endolysins against Gram-negative bacteria is the low permeability of the lipopolysaccharide membrane. Thus, the aim of the present project is to unravel the evolutionary markers selected in the association of phage-endolysin-host ecology in Gram-negative bacteria of clinical interest and to evaluate the antimicrobial activity of broad-spectrum modified endolysins against multiresistant Gram-negative bacteria. Broad-spectrum endolysins will be selected, modified and cloned by comparing the evolutionary rate of species-specific bacteriophage-encoded phage endolysins to the selected bacteria. The antibacterial activity of purified enzymes will be evaluated in vitro and in vivo models of Galleria mellonella and/or BALB/c mice in the presence and absence of permeabilizing agents. This project presents as innovation the search for broad spectrum phage endolysins against multiresistant Gram-negative bacteria by selecting appropriate protein motifs and/or mutation and construction of genetically modified enzymes for exogenous action as possible alternative treatments to infections caused by antibiotic resistant bacteria. (AU)

Scientific publications

(4)

(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)

PARDINI GONTIJO, MARCO TULIO; PEREIRA VIDIGAL, PEDRO MARCUS; SOTO LOPEZ, MARYORIS ELISA; BROCCHI, MARCELO. Bacteriophages that infect Gram-negative bacteria as source of signal-arrest-release motif lysins. Research in Microbiology, v. 172, n. 2, MAR 2021. (17/10051-2, 20/01535-9)

VILAS BOAS CORDEIRO, TAMIRES FERNANDA; PARDINI GONTIJO, MARCO TULIO; JORGE, GENESY PEREZ; BROCCHI, MARCELO. EbfC/YbaB: A Widely Distributed Nucleoid-Associated Protein in Prokaryotes. MICROORGANISMS, v. 10, n. 10, p. 15-pg., 2022-10-01. (17/10051-2, 20/01535-9, 21/00465-0)

PARDINI GONTIJO, MARCO TULIO; JORGE, GENESY PEREZ; BROCCHI, MARCELO. Current Status of Endolysin-Based Treatments against Gram-Negative Bacteria. ANTIBIOTICS-BASEL, v. 10, n. 10, OCT 2021. (20/01535-9, 17/10051-2)

PARDINI GONTIJO, MARCO TULIO; TELES, MATEUS PEREIRA; PEREIRA VIDIGAL, PEDRO MARCUS; BROCCHI, MARCELO. Expanding the Database of Signal-Anchor-Release Domain Endolysins Through Metagenomics. PROBIOTICS AND ANTIMICROBIAL PROTEINS, v. 14, n. 4, p. 10-pg., 2022-05-07. (20/09815-0, 20/01535-9, 21/00465-0)

Academic Publications

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

GONTIJO, Marco Túlio Pardini. Comparative genomics and antimicrobial activity of recombinant phage endolysins against multi-drug resistant bacteria. 2022. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.