Coxiella burnetii utilizes both glutamate and glucose during infection with glucose uptake mediated by multiple transporters
| Autor: | David P De Souza, Dedreia Tull, Saravanan Dayalan, Hayley J. Newton, Fiona M. Sansom, Nitika Neha, Malcolm J. McConville, Miku Kuba, Joshua P M Newson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
carbon metabolism
THP-1 Cells Glucose uptake Virulence Glutamic Acid Biochemistry Microbiology 03 medical and health sciences Bacterial Proteins Host-Microbe Interactions Animals Humans intracellular bacterial pathogen Molecular Biology Research Articles 030304 developmental biology 0303 health sciences biology 030306 microbiology Chemistry Glucose transporter Gluconeogenesis glucose transport Membrane Transport Proteins Biological Transport Cell Biology Metabolism Host cell lysosome Coxiella burnetii biology.organism_classification bacterial infections and mycoses gram-negative bacteria Lepidoptera Metabolic pathway Glucose Host-Pathogen Interactions bacteria Q Fever Glycolysis Intracellular HeLa Cells |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|