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. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Margetis, Dimitri; Roux, Damien; Gaudry, Stéphane; Messika, Jonathan; Bouvet, Odile; Branger, Catherine; Ponnuswamy, Padmapriya; Oufella, Hafid Ait; Dreyfuss, Didier; Denamur, Erick; Ricard, Jean-Damien
• Is Part Of: Critical care medicine. Volume 43:Issue 6(2015)
• Publication Date: 2015-06
• Subjects: Critical care medicine -- Periodicals; Soins intensifs -- Périodiques; 616.028
• DOI: 10.1097/CCM.0000000000000972
• Languages: English
• ISSNs: 0090-3493

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>In the context of increasing microbial resistance and limited new antimicrobials, we aimed to study the antimicrobial effects of cranberry proanthocyanidin extracts on <italic>Escherichia coli</italic> growth, adhesion to epithelial cells, and lung infection.</p> </sec> <sec> <title>Design:</title> <p>Experimental in vitro and in vivo investigation.</p> </sec> <sec> <title>Setting:</title> <p>University research laboratory.</p> </sec> <sec> <title>Subjects:</title> <p>Seventy-eight 6- to 8-week-old male Balb/C mice.</p> </sec> <sec> <title>Interventions:</title> <p>In vitro, the effect of increasing concentrations of cranberry proanthocyanidin on bacterial growth of different clinical <italic>E. coli</italic> isolates was evaluated. Ex vivo, adhesion of <italic>E. coli</italic> 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 <italic>E. coli</italic> precultured with or without cranberry proanthocyanidin. <italic>E. coli</italic> isolates originated from ventilated ICU patients with respiratory tract colonization or ventilator- associated pneumonia. They differed in number of virulence genes.</p> </sec> <sec> <title>Measurements and Main Results:</title> <p>A significant inhibition of bacterial growth was observed with increasing concentration of cranberry proanthocyanidin, affecting both time to maximal growth and maximal growth rate (<italic>p</italic> < 0.0001 for both). The minimal concentration at which this effect occurred was 250 μg/mL. Cranberry proanthocyanidin significantly reduced <italic>E. coli</italic> adhesion to fresh buccal epithelial cells by up to 80% (<italic>p</italic> < 0.001). Bacterial counts in homogenized lungs and bronchoalveolar lavage fluid were decreased after cranberry proanthocyanidin exposition (<italic>p</italic> < 0.05 and <italic>p</italic> < 0.01, respectively). Cranberry proanthocyanidin also decreased KC concentrations and polymorphonuclear cell recruitment in bronchoalveolar lavage fluid (<italic>p</italic> < 0.05 for both). At identical inoculum, mortality was reduced by more than half in mice inoculated with <italic>E. coli</italic> exposed to cranberry proanthocyanidin (<italic>p</italic> < 0.01).</p> </sec> <sec> <title>Conclusion:</title> <p>Cranberry proanthocyanidins exhibit potent effects on growth, adhesion, and virulence of oropharyngeal and lung isolates of <italic>E. coli</italic>, suggesting that cranberry proanthocyanidin could be of clinical interest to reduce oropharyngeal colonization and prevent lung infection.</p> </sec> </abstract>