Increased airway glucose increases airway bacterial load in hyperglycaemia.
Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes.
Mucosal Infection &Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, W2 1PG, UK.|MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Simren K
SK
Gill
MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Kailyn
K
Hui
Airway Disease Infection Section, National Heart &Lung Institute, Imperial College London, London, W2 1PG, UK.
Hugo
H
Farne
Institute for Infection and Immunity, St George's, University of London, London SW17 0RE, UK.
James P
JP
Garnett
Institute for Infection and Immunity, St George's, University of London, London SW17 0RE, UK.
Deborah L
DL
Baines
Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Imperial College London, Hammersmith Campus, London W12 0HS, UK.
Luke S P
LS
Moore
Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance, Imperial College London, Hammersmith Campus, London W12 0HS, UK.
Alison H
AH
Holmes
MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Alain
A
Filloux
Mucosal Infection &Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London, W2 1PG, UK.
John S
JS
Tregoning
D000328:Adult; D000368:Aged; D000818:Animals; D001424:Bacterial Infections / Q000209:etiology* / Q000378:metabolism* / Q000382:microbiology; D058491:Bacterial Load; D001786:Blood Glucose; D016638:Critical Illness; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D005798:Genes, Bacterial; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000150:complications*; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D020545:Respiratory Mucosa / Q000378:metabolism / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000209:etiology* / Q000378:metabolism* / Q000382:microbiology
D001786:Blood Glucose; D005947:Glucose