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Interactions between Francisella tularensis and Hepatocytes
Author(s) -
Thomas Cindy A.,
Furie Martha
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.252.1
Subject(s) - francisella tularensis , tularemia , virulence , francisella , microbiology and biotechnology , bacteria , biology , intracellular parasite , pathogen , virology , intracellular , attenuated vaccine , genetics , gene
Francisella tularensis is a facultative intracellular bacterium and the etiological agent of tularemia. This pathogen is classified as a category A agent of bioterrorism. Regardless of the route of transmission, the liver is an important target of infection in tularemia, and F. tularensis grows to high numbers within hepatocytes, the major cell type of this organ. This study investigates the mechanisms that influence the uptake and replication of F. tularensis in hepatocytes. The study was performed with F. tularensis Live Vaccine Strain (LVS) and the highly virulent Schu S4 strain, the murine AML‐12 and human HH4 hepatocytic cell lines, and primary mouse hepatocytes. We observed that both heat‐killed and formalin‐fixed bacteria were readily ingested by the hepatocytes. Treatment of the bacteria with chloramphenicol also had no effect on uptake. Primary hepatocytes were less efficient at taking up bacteria compared with the cell lines. Notably, the Schu S4 grew more extensively than the LVS in primary hepatocytes. We have generated a collection of transposon mutants of the LVS and are screening it to identify bacterial factors needed for uptake and replication in hepatocytes. In summary, our results show that uptake of the LVS by hepatocytes is a passive process on the part of the bacterium. Furthermore, the ability of this organism to replicate in hepatocytes may be linked to virulence. NIAID T32 A1007539, P01 AI055621