Management of Enterococcus faecalis biofilms: a combinatorial approach with phytochemical

Area of Science:

• Microbiology
• Pharmacology
• Natural Products Chemistry

Background:

• Antimicrobial resistance in Enterococcus faecalis is a growing concern, largely driven by robust biofilm formation.
• Natural phytochemicals offer a promising avenue for developing novel antimicrobial and antibiofilm strategies.

Purpose of the Study:

• To evaluate the pharmacological, antimicrobial, and antibiofilm potential of cuminaldehyde and thymoquinone, both individually and in combination, against E. faecalis.
• To investigate the underlying mechanisms of action for the observed antibiofilm effects.

Main Methods:

• In silico analysis for pharmacokinetic properties (oral bioavailability, GI absorption, solubility, drug-likeness).
• In vitro antimicrobial assays to determine minimum inhibitory concentrations (MIC) and fractional inhibitory concentration (FIC) index.
• Assessment of antibiofilm activity, extracellular polymeric substance (EPS) production, and protein content.
• Evaluation of reactive oxygen species (ROS) generation and membrane permeability.

Main Results:

• In silico analysis predicted favorable pharmacokinetic profiles for both cuminaldehyde and thymoquinone.
• The combination exhibited an additive antimicrobial effect (FIC index = 0.73).
• Combined sub-MIC doses significantly reduced E. faecalis biofilm formation (approx. 80%), EPS production (approx. 76%), and protein content (approx. 70%).
• Antibiofilm activity was linked to increased ROS accumulation and enhanced membrane permeability.

Conclusions:

• The combination of cuminaldehyde and thymoquinone demonstrates significant antimicrobial and potent antibiofilm activity against E. faecalis.
• This synergistic effect suggests a promising therapeutic strategy for managing biofilm-related E. faecalis infections.
• Further research into these natural compounds could lead to improved treatment outcomes for resistant infections.