Outer membrane vesicles carrying violacein and their antibacterial activity to Staphylococcus aureus

• Grant number: 25/00760-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Marcelo Brocchi
• Grantee: Júlia Cascaldi Miranda
• 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

Infections caused by Staphylococcus aureus represent a significant public health challenge whose history is based on the search for new antibiotics, as this bacterium has constantly acquired resistance to them. In the search for new antimicrobial drugs, violacein, a pigment produced by different species of Gram-negative bacteria, has antimicrobial action against Gram-positive bacteria, particularly S. aureus. An issue to be considered when using violacein as an antibacterial is the toxicity of this molecule to eukaryotic cells, despite complying with Lipinski´s rules. One way to overcome toxicity is the development of violacein encapsulation strategies, seeking to reduce its concentration in therapy. Escherichia coli and Salmonella enterica mutant strains for the tolRA genes exhibit a hypervesiculated phenotype,with increased formation of outer membrane vesicles (OMVs). The introduction of mutations in the msbB gene reduces toxicity due to the modification in lipid A of LPS, enhancing the capacity of vesicles produced by these bacteria to carry violacein. Therefore, OMVs produced by ¿tolRA and ¿msbB mutants represent a promising strategy for producing vesicles carrying violacein in the treatment of S. aureus infections. This project aims to explore this strategy, using microbiology and molecular biology techniques.