title: Legionella pneumophila multiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells.
abstract: Human 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 AMPKalpha subunit. Conversely, mitochondrial dysfunction is phenocopied, and intracellular Legionella growth is enhanced, by overexpressing an active form of AMPKalpha in otherwise normal cells. These results indicate that AMPK signalling in response to mitochondrial dysfunction enhances Legionella proliferation in host cells.
authors.affiliation: Department of Microbiology, La Trobe University, VIC 3086, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Francione
authors.forename: Paige K
authors.initials: PK
authors.lastname: Smith
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Accari
authors.forename: Philip E
authors.initials: PE
authors.lastname: Taylor
authors.forename: Paul B
authors.initials: PB
authors.lastname: Bokko
authors.forename: Salvatore
authors.initials: S
authors.lastname: Bozzaro
authors.forename: Peter L
authors.initials: PL
authors.lastname: Beech
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fisher
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001424:Bacterial Infections / Q000382:microbiology; D002455:Cell Division; D049109:Cell Proliferation; D018834:Chaperonin 60 / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000382:microbiology; D004023:Dictyostelium / Q000166:cytology / Q000201:enzymology / Q000382:microbiology* / Q000648:ultrastructure; D016952:Legionella pneumophila / Q000166:cytology* / Q000254:growth & development / Q000648:ultrastructure; D008928:Mitochondria / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology*; D016372:RNA, Antisense / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D018834:Chaperonin 60; D016372:RNA, Antisense; D055372:AMP-Activated Protein Kinases