Open AccessLipidation of the FPI protein I gl E contributes to F rancisella tularensis ssp. novicida intramacrophage replication and virulence
Author(s) -
Nguyen Jesse Q.,
Gilley Ryan P.,
Zogaj Xhavit,
Rodriguez Stephen A.,
Klose Karl E.
Publication year - 2014
Publication title -
pathogens and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.983
H-Index - 105
ISSN - 2049-632X
DOI - 10.1111/2049-632x.12167
Subject(s) - francisella tularensis , francisella , tularemia , bacterial outer membrane , biology , secretion , virulence , periplasmic space , type vi secretion system , microbiology and biotechnology , pathogenicity island , genetics , gene , escherichia coli , biochemistry
Francisella tularensis is a Gram‐negative bacterium responsible for the human disease tularemia. The Francisella pathogenicity island (FPI) encodes a secretion system related to type VI secretion systems (T6SS) which allows F. tularensis to escape the phagosome and replicate within the cytosol of infected macrophages and ultimately cause disease. A lipoprotein is typically found encoded within T6SS gene clusters and is believed to anchor portions of the secretion apparatus to the outer membrane. We show that the FPI protein IglE is a lipoprotein that incorporates 3 H‐palmitate and localizes to the outer membrane. A C22G IglE mutant failed to be lipidated and failed to localize to the outer membrane, consistent with C22 being the site of lipidation. Francisella tularensis ssp. novicida expressing IglE C22G is defective for replication in macrophages and unable to cause disease in mice. Bacterial two‐hybrid analysis demonstrated that IglE interacts with the C‐terminal portion of the FPI inner membrane protein PdpB, and PhoA fusion analysis indicated the PdpB C‐terminus is located within the periplasm. We predict this interaction facilitates channel formation to allow secretion through this system.