Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth.
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.
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Aria
A
Eshraghi
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Jungyun
J
Kim
Department of Biochemistry, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Alexandra C
AC
Walls
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Hannah E
HE
Ledvina
Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA 99164, USA.
Cheryl N
CN
Miller
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kathryn M
KM
Ramsey
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
John C
JC
Whitney
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Matthew C
MC
Radey
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
S Brook
SB
Peterson
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Brittany R
BR
Ruhland
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
Bao Q
BQ
Tran
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
Young Ah
YA
Goo
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
David R
DR
Goodlett
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Simon L
SL
Dove
Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA 99164, USA.
Jean
J
Celli
Department of Biochemistry, School of Medicine, University of Washington, Seattle, WA 98195, USA.
David
D
Veesler
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, School of Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: mougous@u.washington.edu.
Joseph D
JD
Mougous
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005604:Francisella tularensis / Q000235:genetics* / Q000254:growth & development*; D044404:Genomic Islands; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000382:microbiology*; D021381:Protein Transport; D000069376:Type VI Secretion Systems; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D000069376:Type VI Secretion Systems; D037521:Virulence Factors