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Biochem J. 2019 Sep 16. pii: BCJ20190504. doi: 10.1042/BCJ20190504. [Epub ahead of print]

Coxiella burnetii utilizes both glutamate and glucose during infection with glucose uptake mediated by multiple transporters.

Author information

1
Department of Microbiology and Immunology, University of Melbourne, Doherty Institute, 792 Elizabeth Street, Melbourne, Australia.
2
Melbourne Veterinary School, University of Melbourne, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Australia.
3
Metabolomics Australia, University of Melbourne, Bio21 Institute, Melbourne, Australia.
4
The Bio21 Molecular Science and Biotechnology Institute, Metabolomics Australia, The University of Melbourne, Parkville, Australia.
5
University of Melbourne, Melbourne, Australia.
6
Department of Microbiology and Immunology, University of Melbourne, Doherty Institute, 792 Elizabeth Street, Melbourne, Australia hnewton@unimelb.edu.au.

Abstract

Coxiella burnetii is a Gram-negative bacterium which causes Q fever, a complex and life‑threatening infection with both acute and chronic presentations. C. burnetii invades a variety of host cell types and replicates within a unique vacuole derived from the host cell lysosome. In order to understand how C. burnetii survives within this intracellular niche, we have investigated the carbon metabolism of both intracellular and axenically cultivated bacteria. Both bacterial populations were shown to assimilate exogenous [13C]glucose or [13C]glutamate, with concomitant labeling of intermediates in glycolysis and gluconeogenesis, and in the TCA cycle. Significantly, the two populations displayed metabolic pathway profiles reflective of the nutrient availabilities within their propagated environments. Disruption of the C. burnetii glucose transporter, CBU0265, by transposon mutagenesis led to a significant decrease in [13C]glucose utilization but did not abolish glucose usage, suggesting that C. burnetii express additional hexose transporters which may be able to compensate for the loss of CBU0265. This was supported by intracellular infection of human cells and in vivo studies in the insect model showing loss of CBU0265 had no impact on intracellular replication or virulence. Using this mutagenesis and [13C]glucose labeling approach, we identified a second glucose transporter, CBU0347, the disruption of which also showed significant decreases in 13C‑label incorporation but did not impact intracellular replication or virulence. Together, these analyses indicate that C. burnetii may use multiple carbon sources in vivo and exhibits greater metabolic flexibility than expected.

KEYWORDS:

Coxiella burnetii; Gram negative bacteria; carbon metabolism; glucose transport; intracellular bacterial pathogen

PMID:
31527117
DOI:
10.1042/BCJ20190504

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