RecA inhibitor epicatechin prolongs the development of fluoroquinolone resistance in Pasteurella multocida

Area of Science:

• Veterinary Microbiology
• Molecular Biology
• Antimicrobial Resistance

Background:

• Pasteurella multocida is a major cause of bovine respiratory disease and exhibits increasing resistance to antibiotics like fluoroquinolones.
• The SOS response is a critical mechanism in the development of bacterial antibiotic resistance.
• Targeting SOS response genes, such as recA and recO, can potentially delay fluoroquinolone resistance in P. multocida.

Purpose of the Study:

• To identify inhibitors of the RecA protein, a key component of the bacterial SOS response.
• To evaluate the efficacy of epicatechin as a RecA inhibitor in preventing fluoroquinolone resistance in P. multocida.
• To assess the combined therapeutic effect of epicatechin and ciprofloxacin against P. multocida.

Main Methods:

• High-throughput molecular docking was employed to screen for potential RecA protein inhibitors.
• In vitro experiments were conducted to test the efficacy of epicatechin in inhibiting fluoroquinolone resistance.
• The antimicrobial efficacy of co-administering epicatechin and ciprofloxacin was evaluated.

Main Results:

• Epicatechin was identified as a significant inhibitor of RecA protein function through molecular docking.
• Epicatechin effectively inhibited the development of fluoroquinolone resistance in P. multocida.
• In vitro studies demonstrated that co-administration of epicatechin and ciprofloxacin enhanced the antimicrobial activity against P. multocida.

Conclusions:

• Epicatechin acts as an effective inhibitor of the RecA protein.
• Combining epicatechin with ciprofloxacin presents a promising strategy for treating fluoroquinolone-resistant P. multocida infections.
• Targeting the SOS response pathway offers a viable approach to combatting antibiotic resistance in veterinary pathogens.