Antibiofilm action of phytochemicals on Enterobacteriaceae

Area of Science:

• Microbiology
• Biochemistry
• Drug Discovery

Background:

• Biofilm-associated infections are a significant health concern, with limited treatment options due to pathogen protection within biofilms.
• The adhesin protein MrkD1P, located on fimbriae tips, is crucial for initiating bacterial adhesion and subsequent biofilm formation.
• Enterobacteriaceae species like E. coli, S. typhi, and K. pneumoniae are major causes of biofilm-related infections.

Purpose of the Study:

• To investigate the potential of plant phenols in inhibiting biofilm formation in key Enterobacteriaceae species.
• To identify specific phenolic compounds that can disrupt the MrkD1P adhesin protein's function.
• To evaluate the efficacy of these compounds in preventing and disintegrating established biofilms.

Main Methods:

• Construction of a homology model for the MrkD1P protein.
• In silico screening of 44 phenolic derivatives for binding affinity to MrkD1P.
• Minimum Biofilm Inhibitory Concentration (MBIC) assays to determine effective compound doses.
• Biofilm inhibition assays and field emission gun scanning electron microscopy (FEG-SEM) to assess biofilm reduction and fimbriae disruption.
• Biofilm re-formation assays to evaluate long-term inhibition.

Main Results:

• Caffeic acid and 3-hydroxybenzoic acid showed the highest binding-free energies with the MrkD1P protein.
• These compounds effectively reduced biofilm formation across tested Enterobacteriaceae species, with over 80% inhibition at specific concentrations.
• FEG-SEM confirmed that the phenolic compounds disintegrated bacterial fimbriae, thereby inhibiting adhesion.
• Inhibition of fimbriae prevented biofilm re-formation on new surfaces.

Conclusions:

• Caffeic acid and 3-hydroxybenzoic acid possess significant antibiofilm properties against Enterobacteriaceae.
• Targeting the MrkD1P adhesin protein with plant-derived phenols is a promising strategy for combating biofilm infections.
• These findings suggest potential therapeutic applications for these compounds in treating bacterial infections associated with Enterobacteriaceae biofilms.