Combating antimicrobial resistance in multidrug-resistant bacteria through photodynamic action

• Grant number: 24/00100-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2024
• Effective date (End): June 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Physics
• Acordo de Cooperação: CNPq - INCTs
• Principal Investigator: Vanderlei Salvador Bagnato
• Grantee: Jennifer Machado Soares
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 14/50857-8 - National Institute in Basic Optics and Applied to Life Sciences, AP.TEM

Abstract

Antimicrobial resistance (AMR) is emerging as a growing concern in scientific research, especially in the face of the exponential spread of multidrug-resistant bacteria (MDR) that defyconventional antibiotics. This project aims to curb the advance of AMR through photodynamicaction, an approach that utilizes photosensitizing molecules combined with light to generatereactive oxygen species, inducing oxidative stress in bacterial cells without discriminating againstmicroorganisms. Previous studies indicate that this photooxidative action can increase bacterialsusceptibility to various antibiotics. However, issues related to the heritability of this resistance breakdown and cellular modifications in the remaining population remain underexplored. Themain objective of this research is to deepen the understanding of the interactions betweenphotodynamic inactivation (PDI), antibiotic therapy, and sonodynamic therapy, exploring theirspecific effects on multidrug-resistant bacteria (MDR), with a special focus on Staphylococcusaureus. Throughout the project, protocols for breaking AMR will be optimized, using curcumin asa photosensitizing and sonophotosensitizing molecule. Population effects will be assessed through survival curves, followed by mathematical models. Heritability studies, accompanying different bacterial growth cycles, will be conducted using advanced techniques such as confocal microscopy and high-resolution oximetry (OROBOROS Oxygraph-2k, Austria) to analyze cellular metabolism. The expected results of this project have the potential to positively impact clinical practice, providing innovative and effective alternatives in the treatment of multidrug-resistant infections, thus representing a significant advancement in therapeutic approaches. (AU)