EVALUATION OF THE ANTIMICROBIAL ACTIVITY OF THE COMBINATION OF NISIN AND SIMVASTATIN AGAINST S. AUREUS AND E. COLI

• Grant number: 24/21572-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Karina Cogo Müller
• Grantee: Manuela Afonso Lara
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/16461-6 - Effect of Nisin and Lactoferrin on the viability and production of volatile sulfur compounds in oral bacteria and development of chitosan nanoparticles as a sustained release system for topical oral application, AP.R

Abstract

Antimicrobial resistance (AMR) is one of the biggest global threats to public health, especially due to microorganisms such as Escherichia coli and Staphylococcus aureus, which are among the main resistant pathogens. These microorganisms employ various resistance mechanisms, including the production of beta-lactamases and structural alterations to the cell wall. In this context, therapeutic alternatives such as antimicrobial peptides (nisin) and drugs with antimicrobial effects (simvastatin) have shown promising potential. Nisin acts by inhibiting peptidoglycan synthesis in Gram-positive bacteria, while simvastatin affects cell wall integrity and reduces biofilm formation. Although the combination of these substances has not yet been investigated, it has synergistic potential as it combines different mechanisms of action on the bacterial cell wall and membrane. Therefore, this study aims to evaluate the antimicrobial effects of the combination of nisin and simvastatin against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the substances against methicillin-sensitive S. aureus (MSSA, ATCC 29213), methicillin-resistant S. aureus (MRSA, ATCC 33591), E. coli (ATCC 10536) and extended-spectrum beta-lactamase-producing E. coli (ESBL, ATCC BAA-2326) will be determined. In addition, the effect of the association on biofilm formation will be evaluated using crystal violet staining and scanning electron microscopy, and possible changes in bacterial morphology will be analyzed using transmission electron microscopy. Finally, the expression of genes related to cell wall formation in response to the substances will be investigated. The results of this study could provide relevant insights into new therapeutic approaches to tackling AMR, contributing to the development of more effective strategies against resistant bacterial strains.