@article{f5114ca3859a4d388259b77d0ad495ba,
title = "Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth",
abstract = "The intracellular bacterial pathogen Francisella tularensis causes tularemia, a zoonosis that can be fatal. The type VI secretion system (T6SS) encoded by the Francisella pathogenicity island (FPI) is critical for the virulence of this organism. Existing studies suggest that the complete repertoire of T6SS effectors delivered to host cells is encoded by the FPI. Using a proteome-wide approach, we discovered that the FPI-encoded T6SS exports at least three effectors encoded outside of the island. These proteins share features with virulence determinants of other pathogens, and we provide evidence that they can contribute to intramacrophage growth. The remaining proteins that we identified are encoded within the FPI. Two of these FPI-encoded proteins constitute effectors, whereas the others form a unique complex required for core function of the T6SS apparatus. The discovery of secreted effectors mediating interactions between Francisella and its host significantly advances our understanding of the pathogenesis of this organism.",
author = "Aria Eshraghi and Jungyun Kim and Walls, {Alexandra C.} and Ledvina, {Hannah E.} and Miller, {Cheryl N.} and Ramsey, {Kathryn M.} and Whitney, {John C.} and Radey, {Matthew C.} and Peterson, {S. Brook} and Ruhland, {Brittany R.} and Tran, {Bao Q.} and Goo, {Young Ah} and Goodlett, {David R.} and Dove, {Simon L.} and Jean Celli and David Veesler and Mougous, {Joseph D.}",
note = "Funding Information: The authors would like to thank Tamir Gonen and Hongjin Zheng for preliminary EM analyses, Adelle McFarland for technical advice, Josh Woodward for critical review of the manuscript, Dan Stetson and Brad Cookson for sharing reagents, and members of the J.D.M. lab for helpful discussions. J.C.W. was supported by a postdoctoral research fellowship from CIHR , training grants from the NIH supported A.E. and H.E.L. ( AI055396 ), A.C.W. ( GM008268 ), and K.M.R. ( HD055148 ), and J.D.M. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund ( BWF 1010010 ) and is an HHMI investigator. The work was supported by The University of Maryland Baltimore School of Pharmacy Mass Spectrometry Center ( SOP1841-IQB2014 to Y.A.G. and D.R.G.), the Paul G. Allen School for Global Health, Washington State University (to J.C.), and National Institutes of Health grants AI081693 (to S.L.D.) and AI080609 (to J.D.M.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = nov,
day = "9",
doi = "10.1016/j.chom.2016.10.008",
language = "English (US)",
volume = "20",
pages = "573--583",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}