Premium
Francisella bacteria encode genes required for efficient invasion and intracellular replication in hepatocytes
Author(s) -
Law HT,
Sriram Aarati,
Fevang Charlotte,
Guttman Julian Andrew
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.523.5
Subject(s) - francisella tularensis , francisella , tularemia , intracellular , biology , pathogenicity island , microbiology and biotechnology , gene , intracellular parasite , complementation , bacteria , virulence , mutant , genetics
Francisella tularensis is a bacterium that can cause up to 60% mortality in humans. These microbes carry a cluster of conserved genes present in all F. tularensis subspecies called the Francisella pathogenicity island (FPI). Within the FPI, iglB , iglC , pdpA and vgrG genes are important for intracellular macrophage survival and virulence; yet, their role in epithelial cell infections, a major contributor to the progression of disease, is unclear. Given that F. tularensis uses dissimilar mechanisms to enter different cell types, we hypothesized that FPI genes play a crucial role in bacterial entry into epithelial cells. To test this hypothesis, BNL CL.2 hepatocytes were infected with F. novicida for up to 48 h. Detailed microscopic examination and gentamicin protection assay revealed that Δ iglB , Δ iglC , Δ vgrG , Δ pdpA Francisella mutants were invasion and replication deficient. We showed that gene complementation restored intracellular growth. Our data suggest that IglB, IglC, PdpA and VgrG are important for hepatocyte infections, as they are vital for efficient invasion and intracellular proliferation. Grant Funding Source : NSERC, CIHR