Characterization of Salmonella enterica Typhimurium mutant strains for bacterial chromosome associated proteins.

• Grant number: 25/03800-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Marcelo Brocchi
• Grantee: Luiza Zanini Caram Sfair
• 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

Salmonella enterica Typhimurium is a Gram-negative bacterium belonging to the Enterobacteriaceae family. It is a global public health concern due to its high incidence and severity, causing diseases ranging from gastroenteritis to severe systemic infections. The emergence of multidrug-resistant (MDR) isolates has complicated infection treatment; therefore, it is essential to investigate the mechanisms of this bacterium as potential new targets for its control. In most bacteria, the chromosome is circular, and in E. coli, as well as in S. enterica, it consists of six regions: four macrodomains (OriC, Ter, Left, and Right) and two unstructured regions. A defining characteristic of each macrodomain is its specific interaction with proteins, such as MaoP with OriC, MatP with Ter, and SlmA with all except Ter. In E. coli, MaoP is involved in biofilm formation, and its transcription increases during growth and under stress conditions; SlmA acts as a transcriptional activator of chitobiose in Vibrio cholerae, and MatP functions as an organizer of chromosomal segregation processes. However, these proteins have been scarcely studied in S. enterica. Therefore, this study aims to characterize the phenotype of S. enterica Typhimurium mutants for the genes encoding the MaoP (yifE), MatP (ycbG) and SlmA (slmA) proteins. To achieve this, mutant strains will be constructed through gene deletion and characterized in terms of in vitro growth, motility, and biofilm formation, as well as under various stress conditions. Virulence attenuation of the mutants will be assessed using the Galleria mellonella model and, depending on the results, in mice. As an additional step, RNA-Seq analyses will be performed to characterize the ¿yifE strain. Thus, this study will provide a better characterization of these proteins' functions in S. enterica, validating them as potential targets for the development of inhibitory compounds.