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Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Garnett, JP; Braun, D; McCarthy, AJ; Farrant, MR; Baker, EH; Lindsay, JA; Baines, DL (2014) Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid. Cellular and Molecular Life Sciences, 71 (23). pp. 4665-4673. ISSN 1420-9071 https://doi.org/10.1007/s00018-014-1635-y
SGUL Authors: Baines, Deborah Baker, Emma Harriet Lindsay, Jodi Anne Garnett, James Peter

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Abstract

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection.

Item Type: Article
Additional Information: © The Author(s) 2014 Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Keywords: Biochemistry & Molecular Biology, 0601 Biochemistry And Cell Biology, 0606 Physiology, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Cellular and Molecular Life Sciences
ISSN: 1420-9071
Language: eng
Dates:
DateEvent
9 May 2014Published
PubMed ID: 24810961
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107248
Publisher's version: https://doi.org/10.1007/s00018-014-1635-y

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