Increased airway glucose increases airway bacterial load in hyperglycaemia
File(s)
Accepted version
Published version
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2016-06-08
Date Acceptance
2016-05-19
Citation
Scientific Reports, 2016, 6
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
6
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Wellcome Trust
Engineering & Physical Science Research Council (EPSRC)
National Institute of Health Research Imperial Biomedical Research Centre
Grant Number
RDA02 79560
105603/Z/14/Z
EP/M027007/1
WMNF_P46472
Publication Status
Published
Article Number
27636