title: Francisella tularensis uses cholesterol and clathrin-based endocytic mechanisms to invade hepatocytes.
abstract: Francisella tularensis are highly infectious microbes that cause the disease tularemia. Although much of the bacterial burden is carried in non-phagocytic cells, the strategies these pathogens use to invade these cells remains elusive. To examine these mechanisms we developed two in vitro Francisella-based infection models that recapitulate the non-phagocytic cell infections seen in livers of infected mice. Using these models we found that Francisella novicida exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We also found that the clathrin accessory proteins AP-2 and Eps15 co-localized with invading Francisella novicida as well as the Francisella Live Vaccine Strain (LVS) during hepatocyte infections. Interestingly, caveolin, a protein involved in the invasion of Francisella in phagocytic cells, was not required for non-phagocytic cell infections. These results demonstrate a novel endocytic mechanism adopted by Francisella and highlight the divergence in strategies these pathogens utilize between non-phagocytic and phagocytic cell invasion.
authors.affiliation: Simon Fraser University Department of Biological Sciences Shrum Science Centre Room B8276 Burnaby, BC, V5A 1S6.
authors.forename: H T
authors.initials: HT
authors.lastname: Law
authors.forename: Ann En-Ju
authors.initials: AE
authors.lastname: Lin
authors.forename: Youra
authors.initials: Y
authors.lastname: Kim
authors.forename: Brian
authors.initials: B
authors.lastname: Quach
authors.forename: Francis E
authors.initials: FE
authors.lastname: Nano
authors.forename: Julian Andrew
authors.initials: JA
authors.lastname: Guttman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D022461:Caveolins / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D005260:Female; D005604:Francisella tularensis / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015233:Models, Statistical; D010587:Phagocytosis; D010873:Pinocytosis; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014406:Tularemia / Q000382:microbiology* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D022461:Caveolins; D002966:Clathrin; C082729:Eps15 protein, mouse; D050656:Transcription Factor AP-2; D002784:Cholesterol