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Francisella enters host cells by Clathrin‐mediated endocytosis at a cholesterol rich domain
Author(s) -
Lin Ann E,
Kim Youra,
Law HT,
Nano Francis E,
Guttman Julian A
Publication year - 2012
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.26.1_supplement.522.4
Subject(s) - francisella tularensis , francisella , endocytosis , tularemia , biology , clathrin , microbiology and biotechnology , immune system , endocytic cycle , internalization , immunology , cell , gene , virulence , biochemistry , genetics
Francisella tularensis are highly infectious bacterial pathogens that cause a type of acute debilitating febrile illness called tularemia. While Francisella reportedly colonize and establish infection in multiple organs, the liver remains as the primary site of infections. Although these infections are responsible for the mortality of 35% of infected individuals if left untreated, the strategies these pathogens use to invade non‐phagocytic cells remain elusive. Therefore, our objective is to examine the subcellular mechanisms these bacteria utilize to infect their hosts. We generated the hypothesis that Francisella co‐opt normal human endocytic machinery to internalize into host epithelial cells. To test this, we developed two in vitro Francisella‐ based infection models using murine hepatocyte epithelial cells. By using a combination of pharmacological inhibitors, RNA interference‐mediated protein knock down and protein immunolocalization, we showed that Francisella exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We conclude that this is the first study demonstrating the importance and significance of clathrin‐mediated endocytosis to facilitate efficient Francisella invasion into non‐phagocytic cells. Grant Funding Source: CIHR