Patkee, WR; Carr, G; Baker, EH; Baines, DL; Garnett, JP
(2016)
Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.
Journal of Cellular and Molecular Medicine, 20 (4).
pp. 758-764.
ISSN 1582-4934
https://doi.org/10.1111/jcmm.12784
SGUL Authors: Baines, Deborah Baker, Emma Harriet
Abstract
Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.
Item Type: |
Article
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Additional Information: |
© 2016 The Authors.
Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited |
Keywords: |
AMPK, P. aeruginosa, airway epithelium, claudin-1, diabetes, glucose, metformin, occludin, respiratory infection, tight junctions, Biochemistry & Molecular Biology, 0304 Medicinal And Biomolecular Chemistry, 0601 Biochemistry And Cell Biology, 1103 Clinical Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Journal of Cellular and Molecular Medicine |
ISSN: |
1582-4934 |
Language: |
ENG |
Dates: |
Date | Event |
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15 March 2016 | Published | 2 February 2016 | Published Online | 7 December 2015 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
26837005 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/107580 |
Publisher's version: |
https://doi.org/10.1111/jcmm.12784 |
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