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Metformin restricts the basolateral glucose dependent growth of apical Staphylococcus aureus in airway epithelia‐bacteria co‐cultures
Author(s) -
Garnett James Peter,
Naik Sonam,
Baker Emma,
Baines Deborah L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.885.22
Subject(s) - staphylococcus aureus , paracellular transport , metformin , respiratory epithelium , glucose transporter , glucose uptake , endocrinology , medicine , microbiology and biotechnology , chemistry , respiratory system , biology , diabetes mellitus , bacteria , insulin , biochemistry , genetics , membrane , permeability (electromagnetism)
Glucose concentration in the airway surface liquid (ASL) is normally ~12.5 times lower than blood. In patients, raised ASL glucose increases the risk of respiratory infection, particularly with methicillin‐resistant Staphylococcus aureus . We investigated the relationship between basolateral glucose concentration and apical S. aureus growth using an in vitro model of human airway epithelium to test whether metformin (drug used to lower blood glucose) affected this relationship. H441 epithelial cells grown at air‐liquid‐interface were inoculated with 5×10 5 CFU/cm 2 S. aureus (8325‐4) on the apical surface for 7 hours. The transepithelial electrical resistance (TEER) was significantly reduced (P<0.05, n=4) and paracellular glucose flux across H441 monolayers (assessed using 14 C‐L‐glucose) was greatly enhanced (P<0.001, n=4), following S. aureus addition. In addition, apical S. aureus growth (determined by Miles‐Misra) increased with basolateral glucose concentration (10, 20, 40 mM). A 12h pre‐treatment of H441 cells with metformin (1mM) significantly prevented both the reduction in TEER (P<0.001, n=4) and the increase in glucose flux (P<0.0001, n=4), as well as impairing the growth of S. aureus (P<0.05, n=4). These results indicate that metformin restricted apical S. aureus growth in airway co‐cultures by reducing the paracellular diffusion of glucose into the ASL.