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

Biofouling. 2017 Jan;33(1):14-23. doi: 10.1080/08927014.2016.1259415. Epub 2016 Nov 28.

Abstract

Pasteurella multocida (Pm) is the causative agent of atrophic rhinitis in swine. This study aimed to discover biofilm inhibitors against swine Pm to counteract antibiotic resistance and decrease virulence. The virulence factor outer membrane protein A (OmpA) was targeted. A library of drugs approved by the Food and Drug Administration (FDA) was used to perform virtual screening against PmOmpA. The top-scoring compounds had no effect on the growth of Pm serotype A or D. Mycophenolate mofetil showed the highest efficacy in inhibiting biofilm formation by Pm serotype A, with an IC50 of 7.3 nM. For Pm serotype D, indocyanine green showed the highest effect at an IC50 of 11.7 nM. Nevertheless, these compounds had no effect on an established biofilm of Pm. This study offers an alternative way to prevent biofilm formation by Pm that could also be applied to other pathogens.

Keywords: FDA-approved drugs; Pasteurella multocida; biofilm formation; outer membrane protein A; virtual screening.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Outer Membrane Proteins / antagonists & inhibitors*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Indocyanine Green / pharmacology*
  • Models, Biological
  • Models, Molecular
  • Mycophenolic Acid / pharmacology*
  • Pasteurella Infections / drug therapy
  • Pasteurella Infections / microbiology*
  • Pasteurella multocida / drug effects*
  • Pasteurella multocida / metabolism
  • Pasteurella multocida / pathogenicity
  • Pasteurella multocida / physiology
  • Protein Binding
  • Rhinitis, Atrophic / drug therapy
  • Rhinitis, Atrophic / microbiology*
  • Swine
  • Virulence
  • Virulence Factors / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Virulence Factors
  • OMPA outer membrane proteins
  • Mycophenolic Acid
  • Indocyanine Green