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Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication.

Publication ,  Journal Article
Larson, CL; Beare, PA; Voth, DE; Howe, D; Cockrell, DC; Bastidas, RJ; Valdivia, RH; Heinzen, RA
Published in: Infect Immun
February 2015

The intracellular bacterial pathogen Coxiella burnetii directs biogenesis of a parasitophorous vacuole (PV) that acquires host endolysosomal components. Formation of a PV that supports C. burnetii replication requires a Dot/Icm type 4B secretion system (T4BSS) that delivers bacterial effector proteins into the host cell cytosol. Thus, a subset of T4BSS effectors are presumed to direct PV biogenesis. Recently, the PV-localized effector protein CvpA was found to promote C. burnetii intracellular growth and PV expansion. We predict additional C. burnetii effectors localize to the PV membrane and regulate eukaryotic vesicle trafficking events that promote pathogen growth. To identify these vacuolar effector proteins, a list of predicted C. burnetii T4BSS substrates was compiled using bioinformatic criteria, such as the presence of eukaryote-like coiled-coil domains. Adenylate cyclase translocation assays revealed 13 proteins were secreted in a Dot/Icm-dependent fashion by C. burnetii during infection of human THP-1 macrophages. Four of the Dot/Icm substrates, termed Coxiella vacuolar protein B (CvpB), CvpC, CvpD, and CvpE, labeled the PV membrane and LAMP1-positive vesicles when ectopically expressed as fluorescently tagged fusion proteins. C. burnetii ΔcvpB, ΔcvpC, ΔcvpD, and ΔcvpE mutants exhibited significant defects in intracellular replication and PV formation. Genetic complementation of the ΔcvpD and ΔcvpE mutants rescued intracellular growth and PV generation, whereas the growth of C. burnetii ΔcvpB and ΔcvpC was rescued upon cohabitation with wild-type bacteria in a common PV. Collectively, these data indicate C. burnetii encodes multiple effector proteins that target the PV membrane and benefit pathogen replication in human macrophages.

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Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

February 2015

Volume

83

Issue

2

Start / End Page

661 / 670

Location

United States

Related Subject Headings

  • Vacuoles
  • Recombinant Fusion Proteins
  • Q Fever
  • Protein Transport
  • Microbiology
  • Macrophages
  • Humans
  • Host-Pathogen Interactions
  • Hela Cells
  • HeLa Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Larson, C. L., Beare, P. A., Voth, D. E., Howe, D., Cockrell, D. C., Bastidas, R. J., … Heinzen, R. A. (2015). Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication. Infect Immun, 83(2), 661–670. https://doi.org/10.1128/IAI.02763-14
Larson, Charles L., Paul A. Beare, Daniel E. Voth, Dale Howe, Diane C. Cockrell, Robert J. Bastidas, Raphael H. Valdivia, and Robert A. Heinzen. “Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication.Infect Immun 83, no. 2 (February 2015): 661–70. https://doi.org/10.1128/IAI.02763-14.
Larson CL, Beare PA, Voth DE, Howe D, Cockrell DC, Bastidas RJ, et al. Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication. Infect Immun. 2015 Feb;83(2):661–70.
Larson, Charles L., et al. “Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication.Infect Immun, vol. 83, no. 2, Feb. 2015, pp. 661–70. Pubmed, doi:10.1128/IAI.02763-14.
Larson CL, Beare PA, Voth DE, Howe D, Cockrell DC, Bastidas RJ, Valdivia RH, Heinzen RA. Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication. Infect Immun. 2015 Feb;83(2):661–670.

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

February 2015

Volume

83

Issue

2

Start / End Page

661 / 670

Location

United States

Related Subject Headings

  • Vacuoles
  • Recombinant Fusion Proteins
  • Q Fever
  • Protein Transport
  • Microbiology
  • Macrophages
  • Humans
  • Host-Pathogen Interactions
  • Hela Cells
  • HeLa Cells