Evaluating regulatory proteins as drug targets for controlling the growth of Salmonella enterica

• Grant number: 25/00779-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Marcelo Brocchi
• Grantee: Gabriela Guimarães Carvalho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center, AP.CEPID

Abstract

Bacterial infections are quite common and can rapidly progress to more severe cases such as sepsis and bacteremia. Salmonella sp. is a Gram-negative bacterium that is associated with serious infections in humans and other animals. S. enterica is one of the most prevalent foodborne pathogens, and can cause everything from gastroenteritis to serious systemic infections. The serovars Typhimurium, Enteritidis and Typhi are among the most frequently associated with infection in humans, frequently presenting the multidrug resistance (MDR) phenotype, leading to major impacts on public health. This bacterium has pathogenicity and virulence mechanisms related to its ability to invade intestinal cells, causing gastroenteritis and/or serious systemic infections. Fis is a nucleoid-associated protein (NAP) that plays a fundamental role in the physiology of S. enterica. However, this NAP has been little studied in other serovars, such as Enteritidis and Typhi. Furthermore, there are no data on the global gene regulation of this NAP in S. Enteritidis and S. Typhi. H-NS is a NAP with several functions and is capable of inhibiting virulence genes in S. enterica. Some studies have explored NAPs as drug targets. Thus, one of the objectives of this project is to better understand the function of the Fis protein in serovars Enteritidis and Typhi, unraveling its role in bacterial physiology. In addition, Fis and H-NS will be validated as target proteins for the development of new drugs to control infections by S. enterica serovars Typhimurium, Enteritidis and Typhi. Considering that the outer membrane is an important barrier to the entry of antimicrobials into Gram-negative bacteria, this project will also explore the use of permeabilizing agents, such as beta-amino polyesters (PBAEs), seeking to potentiate the action of antimicrobials on S. enterica. In addition, compounds with detected antimicrobial activity will also be evaluated against S. enterica. (AU)