Photodynamic inactivation increases cell death rate on persistent Staphylococcus aureus.

Area of Science:

• Microbiology
• Antimicrobial Resistance
• Photodynamic Therapy

Background:

• Bacterial persistence is a key factor in chronic and recurrent infections, characterized by dormant subpopulations tolerant to antibiotics.
• Staphylococcus aureus is a significant pathogen where persistence contributes to severe infections.
• Photodynamic inactivation (PDI) uses reactive oxygen species (ROS) for microbial eradication.

Purpose of the Study:

• To investigate persistence formation in S. aureus.
• To evaluate the impact of PDI with curcumin on bacterial persistence and antibiotic susceptibility.
• To understand the influence of bacterial recovery dynamics on treatment efficacy.

Main Methods:

• Time-kill assays with oxacillin to identify biphasic killing curves indicative of persistence.
• Heritability testing to determine the phenotypic nature of persistence.
• Photodynamic inactivation (PDI) using curcumin and blue light (450 nm) followed by viability assessments.
• Post-PDI time-kill assays after metabolic recovery.

Main Results:

• Oxacillin time-kill assays confirmed biphasic killing, indicative of phenotypic persistence in S. aureus.
• PDI with curcumin reduced bacterial viability in a dose-dependent manner.
• Surviving populations after PDI showed transient tolerance-like behavior (unchanged MICs), suggesting PDI may induce dormancy.
• Post-PDI treatment, after metabolic recovery, led to increased antibiotic susceptibility.
• Methicillin-resistant S. aureus (MRSA) exhibited reduced persistence induction, potentially due to stronger oxidative stress defenses.

Conclusions:

• PDI can induce a transient dormant state in S. aureus, affecting antibiotic susceptibility.
• The timing of antibiotic administration relative to PDI is critical for therapeutic outcomes.
• Understanding bacterial adaptation post-PDI is crucial for optimizing treatment strategies against persistent infections.