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Original article
Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose
  1. James P Garnett1,
  2. Emma H Baker1,
  3. Sonam Naik1,
  4. Jodi A Lindsay2,
  5. Gwenan M Knight2,
  6. Simren Gill3,
  7. John S Tregoning2,3,
  8. Deborah L Baines1
  1. 1Division of Biomedical Sciences, Centre for Cell Physiology and Pharmacology, St George's, University of London, London, UK
  2. 2Division of Clinical Sciences, Centre for Infection and Immunity, St George's, University of London, London, UK
  3. 3Mucosal Infection and Immunity, Section of Infectious Diseases, Imperial College London, London, UK
  1. Correspondence to Dr Deborah L Baines, Division of Biomedical Sciences, St George's, University of London, Cranmer Terrace, Tooting, London SW17 0RE, UK; d.baines{at}


Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection.

Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship.

Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected.

Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas.

Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection.

  • Airway Epithelium
  • Bacterial Infection
  • COPD Exacerbations
  • Respiratory Infection

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