Salmonella enterica and Membrane Vesicles (MVs) in Vaccine Development

• Grant number: 23/03213-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2024
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Marcelo Brocchi
• Grantee: Marina Flóro e Silva
• 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 is an important pathogen for humans and other animals causing since enteric to severe systemic infections. After oral ingestion, S. enterica can bind, proliferate, and invade the intestinal mucosa cells. Depending on the bacterial serovar and the host susceptibility, the infection can remain localized to the intestinal subepithelial mucosa or can progress to a systemic infection. However, S. enterica virulence can be attenuated by the deletion of specific target genes. The attenuated strains are good carriers of antigens, DNA and even RNA-based vaccines been able to carry and present macromolecules to cells of the immune system. In addition, S. enterica can be modified to produce a hypervesiculation phenotype (high level of MVs production). Moreover, despite many efforts, few live recombinant attenuated strains are in used nowadays manly due to the challenge in developing strains with appropriate balance between attenuation and immunogenicity. Therefore, the aim of this study is the development of new attenuated strains targeting the deletion of DNA-binding proteins encoding genes with important functions in chromosome structures and DNA topology. Additionally, we will explore the induced attenuation phenotype in which the recombinant strains exhibit a progressive attenuation profile after host infection. We will also explore the use MVs as carrier of DNA vectors, open perspectives for using this approach with RNA-based vectors as well. For this, mutant strains will be constructed exhibiting the hypervesiculating phenotype and a detoxified LPS. At the end of this study, we hope to contribute with the development an innovative platform for vaccine development based on the biotechnological potential of S. enterica