Biofilm inhibitors targeting the outer membrane protein A of Pasteurella multocida in swine

Area of Science:

• Veterinary Microbiology
• Bacterial Pathogenesis
• Drug Discovery

Background:

• Pasteurella multocida (Pm) causes atrophic rhinitis in swine, leading to significant economic losses.
• Antibiotic resistance and virulence of Pm necessitate alternative control strategies.
• Biofilm formation by Pm contributes to its persistence and resistance.

Purpose of the Study:

• To discover novel biofilm inhibitors against swine Pm.
• To target the outer membrane protein A (OmpA) virulence factor.
• To identify compounds that counteract antibiotic resistance and reduce Pm virulence.

Main Methods:

• Virtual screening of FDA-approved drugs against the PmOmpA protein.
• Assessing the efficacy of top-scoring compounds on Pm biofilm formation.
• Determining IC50 values for selected inhibitors against Pm serotypes A and D.

Main Results:

• Mycophenolate mofetil inhibited Pm serotype A biofilm formation (IC50 = 7.3 nM).
• Indocyanine green inhibited Pm serotype D biofilm formation (IC50 = 11.7 nM).
• Identified compounds did not affect bacterial growth or established biofilms.

Conclusions:

• FDA-approved drugs can inhibit Pm biofilm formation, offering a potential alternative to antibiotics.
• Targeting OmpA is a viable strategy for discovering biofilm inhibitors.
• These findings could be extended to control other bacterial pathogens.