title: Effects of Proanthocyanidins on Adhesion, Growth, and Virulence of Highly Virulent Extraintestinal Pathogenic Escherichia coli Argue for Its Use to Treat Oropharyngeal Colonization and Prevent Ventilator-Associated Pneumonia.
abstract: OBJECTIVE
  In the context of increasing microbial resistance and limited new antimicrobials, we aimed to study the antimicrobial effects of cranberry proanthocyanidin extracts on Escherichia coli growth, adhesion to epithelial cells, and lung infection.
  
  
  METHODS
  Experimental in vitro and in vivo investigation.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Seventy-eight 6- to 8-week-old male Balb/C mice.
  
  
  METHODS
  In vitro, the effect of increasing concentrations of cranberry proanthocyanidin on bacterial growth of different clinical E. coli isolates was evaluated. Ex vivo, adhesion of E. coli to fresh human buccal epithelial cells was measured in the presence or absence of cranberry proanthocyanidin using microscopy. In vivo, lung bacterial count, pulmonary immune response (neutrophil murine chemokine keratinocyte-derived cytokine measurement and polymorphonuclear recruitment in bronchoalveolar lavage fluid), and lethality were evaluated in a pneumonia mouse model with E. coli precultured with or without cranberry proanthocyanidin. E. coli isolates originated from ventilated ICU patients with respiratory tract colonization or ventilator- associated pneumonia. They differed in number of virulence genes.
  
  
  RESULTS
  A significant inhibition of bacterial growth was observed with increasing concentration of cranberry proanthocyanidin, affecting both time to maximal growth and maximal growth rate (p<0.0001 for both). The minimal concentration at which this effect occurred was 250 μg/mL. Cranberry proanthocyanidin significantly reduced E. coli adhesion to fresh buccal epithelial cells by up to 80% (p<0.001). Bacterial counts in homogenized lungs and bronchoalveolar lavage fluid were decreased after cranberry proanthocyanidin exposition (p<0.05 and p<0.01, respectively). Cranberry proanthocyanidin also decreased KC concentrations and polymorphonuclear cell recruitment in bronchoalveolar lavage fluid (p<0.05 for both). At identical inoculum, mortality was reduced by more than half in mice inoculated with E. coli exposed to cranberry proanthocyanidin (p<0.01).
  
  
  CONCLUSIONS
  Cranberry proanthocyanidins exhibit potent effects on growth, adhesion, and virulence of oropharyngeal and lung isolates of E. coli, suggesting that cranberry proanthocyanidin could be of clinical interest to reduce oropharyngeal colonization and prevent lung infection.
authors: 1Institut National de la Santé et de la Recherche Médicale, INSERM, IAME, UMR 1137, Paris, France. 2Univ Paris Diderot, Sorbonne Paris Cité, IAME, UMR 1137, Paris, France. 3AP-HP, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier, Colombes, Paris, France. 4Institut National de la Santé et de la Recherche Médicale, INSERM, ECEVE, UMR 1123, Paris, France. 5Univ Paris Diderot, Sorbonne Paris Cité, ECEVE, UMR 1123, Paris, France. 6AP-HP, Service de Microbiologie, Hôpital Louis Mourier, Colombes, Paris, France. 7Institut National de la Santé et de la Recherche Médicale, INSERM, Cardiovascular Research Center, UMR 970, Paris, France. 8Univ Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Dimitri
authors: D
authors: Margetis
authors: Damien
authors: D
authors: Roux
authors: Stéphane
authors: S
authors: Gaudry
authors: Jonathan
authors: J
authors: Messika
authors: Odile
authors: O
authors: Bouvet
authors: Catherine
authors: C
authors: Branger
authors: Padmapriya
authors: P
authors: Ponnuswamy
authors: Hafid Ait
authors: HA
authors: Oufella
authors: Didier
authors: D
authors: Dreyfuss
authors: Erick
authors: E
authors: Denamur
authors: Jean-Damien
authors: JD
authors: Ricard
mesh_terms: D000818:Animals; D001431:Bacteriological Techniques; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D004926:Escherichia coli / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D029799:Vaccinium macrocarpon
chemical_list: D010936:Plant Extracts; D044945:Proanthocyanidins; C013221:proanthocyanidin