title: Effect of rickettsial toxin VapC on its eukaryotic host.
abstract: Rickettsia are intracellular bacteria typically associated with arthropods that can be transmitted to humans by infected vectors. Rickettsia spp. can cause mild to severe human disease with a possible protection effect of corticosteroids when antibiotic treatments are initiated. We identified laterally transferred toxin-antitoxin (TA) genetic elements, including vapB/C, in several Rickettsia genomes and showed that they are functional in bacteria and eukaryotic cells. We also generated a plaque assay to monitor the formation of lytic plaques over time and demonstrated that chloramphenicol accelerates host cell lysis of vapB/C-containing Rickettsia. Whole-genome expression, TUNEL and FISH assays on the infected cells following exposure to the antibiotic revealed early apoptosis of host cells, which was linked to over-transcription of bacterial vapB/C operons and subsequent cytoplasmic VapC toxin release. VapC that is expressed in Escherichia coli and Saccharomyces cerevisiae or microinjected into mammalian cells is toxic through RNase activity and is prevented by dexamethasone. This study provides the first biological evidence that toxin-antitoxin elements act as pathogenic factors in bacterial host cells, confirming comparative genomic evidence of their role in bacterial pathogenicity. Our results suggest that early mortality following antibiotic treatment of some bacterial infections can be prevented by administration of dexamethasone.
authors: Unité des Rickettsies URMITE, UMR CNRS 6236- IRD 198, Marseille, France.
authors: Gilles
authors: G
authors: Audoly
authors: Renaud
authors: R
authors: Vincentelli
authors: Sophie
authors: S
authors: Edouard
authors: Kalliopi
authors: K
authors: Georgiades
authors: Oleg
authors: O
authors: Mediannikov
authors: Grégory
authors: G
authors: Gimenez
authors: Cristina
authors: C
authors: Socolovschi
authors: Jean-Louis
authors: JL
authors: Mège
authors: Christian
authors: C
authors: Cambillau
authors: Didier
authors: D
authors: Raoult
mesh_terms: D017209:Apoptosis; D001427:Bacterial Toxins / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D056890:Eukaryota; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D012281:Rickettsia / Q000472:pathogenicity*
chemical_list: D001427:Bacterial Toxins; D003907:Dexamethasone