taylor-legionellapneumophila-2009.pdf (872.39 kB)
Legionella pneumophila multiplication is enhanced by chronic AMPK signalling in mitochondrially diseased dictyostelium cells
journal contribution
posted on 2009-09-01, 00:00 authored by L Francione, P Smith, S Accari, Philip Taylor, P Bokko, S Bozzaro, Peter BeechPeter Beech, P FisherHuman patients with mitochondrial diseases are more susceptible to bacterial infections, particularly of the respiratory tract. To investigate the susceptibility of mitochondrially diseased cells to an intracellular bacterial respiratory pathogen, we exploited the advantages of Dictyostelium discoideum as an established model for mitochondrial disease and for Legionella pneumophila pathogenesis. Legionella infection of macrophages involves recruitment of mitochondria to the Legionella-containing phagosome. We confirm here that this also occurs in Dictyostelium and investigate the effect of mitochondrial dysfunction on host cell susceptibility to Legionella. In mitochondrially diseased Dictyostelium strains, the pathogen was taken up at normal rates, but it grew faster and reached counts that were twofold higher than in the wild-type host. We reported previously that other mitochondrial disease phenotypes for Dictyostelium are the result of the activity of an energy-sensing cellular alarm protein, AMP-activated protein kinase (AMPK). Here, we show that the increased ability of mitochondrially diseased cells to support Legionella proliferation is suppressed by antisense-inhibiting expression of the catalytic AMPKα subunit. Conversely, mitochondrial dysfunction is phenocopied, and intracellular Legionella growth is enhanced, by overexpressing an active form of AMPKα in otherwise normal cells. These results indicate that AMPK signalling in response to mitochondrial dysfunction enhances Legionella proliferation in host cells.
History
Journal
Disease models and mechanismsVolume
2Issue
9-10Season
September/OctoberPagination
479 - 489Publisher
Company of BiologistsLocation
Cambridge, EnglandPublisher DOI
ISSN
1754-8403eISSN
1754-8411Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2009, Company of BiologistsUsage metrics
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