@article{Garnett:2013:10.1136/thoraxjnl-2012-203178,
author = {Garnett, JP and Baker, EH and Naik, S and Lindsay, JA and Knight, GM and Gill, S and Tregoning, JS and Baines, DL},
doi = {10.1136/thoraxjnl-2012-203178},
journal = {Thorax},
pages = {835--845},
title = {Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose},
url = {http://dx.doi.org/10.1136/thoraxjnl-2012-203178},
volume = {68},
year = {2013}
}

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TY  - JOUR
AB  - Background Diabetes is a risk factor for respiratoryinfection, and hyperglycaemia is associated withincreased glucose in airway surface liquid and risk ofStaphylococcus aureus infection.Objectives To investigate whether elevation ofbasolateral/blood glucose concentration promotes airwayStaphylococcus aureus growth and whether pretreatmentwith the antidiabetic drug metformin affects thisrelationship.Methods Human airway epithelial cells grown atair–liquid interface (±18 h pre-treatment, 30 μM–1 mMmetformin) were inoculated with 5×105 colony-formingunits (CFU)/cm2 S aureus 8325-4 or JE2 orPseudomonas aeruginosa PA01 on the apical surfaceand incubated for 7 h. Wild-type C57BL/6 or db/db(leptin receptor-deficient) mice, 6–10 weeks old, weretreated with intraperitoneal phosphate-buffered saline or40 mg/kg metformin for 2 days before intranasalinoculation with 1×107 CFU S aureus. Mice were culled24 h after infection and bronchoalveolar lavage fluidcollected.Results Apical S aureus growth increased withbasolateral glucose concentration in an in vitro airwayepithelia–bacteria co-culture model. S aureus reducedtransepithelial electrical resistance (RT) and increasedparacellular glucose flux. Metformin inhibited theglucose-induced growth of S aureus, increased RT anddecreased glucose flux. Diabetic (db/db) mice infectedwith S aureus exhibited a higher bacterial load in theirairways than control mice after 2 days and metformintreatment reversed this effect. Metformin did notdecrease blood glucose but reduced paracellular fluxacross ex vivo murine tracheas.Conclusions Hyperglycaemia promotes respiratoryS aureus infection, and metformin modifies glucose fluxacross the airway epithelium to limit hyperglycaemiainducedbacterial growth. Metformin might, therefore, beof additional benefit in the prevention and treatment ofrespiratory infection.
AU  - Garnett,JP
AU  - Baker,EH
AU  - Naik,S
AU  - Lindsay,JA
AU  - Knight,GM
AU  - Gill,S
AU  - Tregoning,JS
AU  - Baines,DL
DO  - 10.1136/thoraxjnl-2012-203178
EP  - 845
PY  - 2013///
SN  - 0040-6376
SP  - 835
TI  - Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose
T2  - Thorax
UR  - http://dx.doi.org/10.1136/thoraxjnl-2012-203178
UR  - http://hdl.handle.net/10044/1/29925
VL  - 68
ER  - 

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