Inactivation of metronidazole by Enterococcus faecalis

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Metronidazole is a key antibiotic for treating anaerobic bacterial infections.
• Enterococcus faecalis and Bacteroides fragilis are common co-pathogens in mixed infections.
• Understanding microbial interactions is crucial for effective antimicrobial therapy.

Purpose of the Study:

• To investigate the in vitro inactivation of metronidazole by clinical isolates of Enterococcus faecalis.
• To determine if Enterococcus faecalis can protect Bacteroides fragilis from metronidazole's effects.

Main Methods:

• Co-culture experiments involving Enterococcus faecalis and Bacteroides fragilis group strains.
• Testing metronidazole inactivation at concentrations 4-8 times the minimum inhibitory concentration (MIC).
• High-performance liquid chromatography (HPLC) to quantify metronidazole levels.
• Analysis of sonicated cell extracts and culture supernatants for inactivation activity.

Main Results:

• All 20 tested Enterococcus faecalis strains protected Bacteroides fragilis from metronidazole.
• Metronidazole was undetectable in culture supernatants after incubation with Enterococcus faecalis.
• A significant increase (4-5 logs) in viable Bacteroides counts was observed in co-cultures.
• Sonicated cell extracts of Enterococcus faecalis inactivated metronidazole, but culture supernatants did not.

Conclusions:

• Enterococcus faecalis possesses the ability to inactivate metronidazole through intracellular mechanisms.
• This inactivation confers significant protection to susceptible Bacteroides fragilis strains.
• The findings highlight a potential mechanism for metronidazole treatment failure in polymicrobial infections involving Enterococcus faecalis.