Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole

ABSTRACT Coxiella burnetii replicates in an acidified lysosome-derived vacuole. Biogenesis of the Coxiella-containing vacuole (CCV) requires bacterial effector proteins delivered into host cells by the Dot/Icm secretion system. Genetic and cell biological analysis revealed that an effector protein c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lara J. Kohler, Shawna R. Reed, Shireen A. Sarraf, David D. Arteaga, Hayley J. Newton, Craig R. Roy
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8bb47c6794e64fadac548e48b9bdf846
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8bb47c6794e64fadac548e48b9bdf846
record_format	dspace
spelling	oai:doaj.org-article:8bb47c6794e64fadac548e48b9bdf8462021-11-15T15:50:19ZEffector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole10.1128/mBio.01127-162150-7511https://doaj.org/article/8bb47c6794e64fadac548e48b9bdf8462016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01127-16https://doaj.org/toc/2150-7511ABSTRACT Coxiella burnetii replicates in an acidified lysosome-derived vacuole. Biogenesis of the Coxiella-containing vacuole (CCV) requires bacterial effector proteins delivered into host cells by the Dot/Icm secretion system. Genetic and cell biological analysis revealed that an effector protein called Cig2 promotes constitutive fusion of autophagosomes with the CCV to maintain this compartment in an autolysosomal stage of maturation. This distinguishes the CCV from other pathogen-containing vacuoles that are targeted by the host autophagy pathway, which typically confers host resistance to infection by delivering the pathogen to a toxic lysosomal environment. By maintaining the CCV in an autolysosomal stage of maturation, Cig2 enabled CCV homotypic fusion and enhanced bacterial virulence in the Galleria mellonella (wax moth) model of infection by a mechanism that decreases host tolerance. Thus, C. burnetii residence in an autolysosomal organelle alters host tolerance of infection, which indicates that Cig2-dependent manipulation of a lysosome-derived vacuole influences the host response to infection. IMPORTANCE Coxiella burnetii is an obligate, intracellular bacterial pathogen that replicates inside a unique, lysosome-like compartment called the Coxiella-containing vacuole (CCV). Over 130 bacterial effector proteins are delivered into the host cell cytosol by the C. burnetii Dot/Icm type IV secretion system. Although the Dot/Icm system is essential for pathogenesis, the functions of most effectors remain unknown. Here we show that the effector protein Cig2 is essential for converting the CCV to an organelle that is similar to the autolysosome. Cig2 function promotes constitutive fusion between the CCV and autophagosomes generated by selective autophagy. Cig2-directed biogenesis of an autolysosomal vacuole is essential for the unique fusogenic properties of the CCV and for virulence in an animal model of disease. This work highlights how bacterial subversion of the host autophagy pathway can influence the cell biological properties of the CCV and influence the host response to infection.Lara J. KohlerShawna R. ReedShireen A. SarrafDavid D. ArteagaHayley J. NewtonCraig R. RoyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Lara J. Kohler Shawna R. Reed Shireen A. Sarraf David D. Arteaga Hayley J. Newton Craig R. Roy Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole
description	ABSTRACT Coxiella burnetii replicates in an acidified lysosome-derived vacuole. Biogenesis of the Coxiella-containing vacuole (CCV) requires bacterial effector proteins delivered into host cells by the Dot/Icm secretion system. Genetic and cell biological analysis revealed that an effector protein called Cig2 promotes constitutive fusion of autophagosomes with the CCV to maintain this compartment in an autolysosomal stage of maturation. This distinguishes the CCV from other pathogen-containing vacuoles that are targeted by the host autophagy pathway, which typically confers host resistance to infection by delivering the pathogen to a toxic lysosomal environment. By maintaining the CCV in an autolysosomal stage of maturation, Cig2 enabled CCV homotypic fusion and enhanced bacterial virulence in the Galleria mellonella (wax moth) model of infection by a mechanism that decreases host tolerance. Thus, C. burnetii residence in an autolysosomal organelle alters host tolerance of infection, which indicates that Cig2-dependent manipulation of a lysosome-derived vacuole influences the host response to infection. IMPORTANCE Coxiella burnetii is an obligate, intracellular bacterial pathogen that replicates inside a unique, lysosome-like compartment called the Coxiella-containing vacuole (CCV). Over 130 bacterial effector proteins are delivered into the host cell cytosol by the C. burnetii Dot/Icm type IV secretion system. Although the Dot/Icm system is essential for pathogenesis, the functions of most effectors remain unknown. Here we show that the effector protein Cig2 is essential for converting the CCV to an organelle that is similar to the autolysosome. Cig2 function promotes constitutive fusion between the CCV and autophagosomes generated by selective autophagy. Cig2-directed biogenesis of an autolysosomal vacuole is essential for the unique fusogenic properties of the CCV and for virulence in an animal model of disease. This work highlights how bacterial subversion of the host autophagy pathway can influence the cell biological properties of the CCV and influence the host response to infection.
format	article
author	Lara J. Kohler Shawna R. Reed Shireen A. Sarraf David D. Arteaga Hayley J. Newton Craig R. Roy
author_facet	Lara J. Kohler Shawna R. Reed Shireen A. Sarraf David D. Arteaga Hayley J. Newton Craig R. Roy
author_sort	Lara J. Kohler
title	Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole
title_short	Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole
title_full	Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole
title_fullStr	Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole
title_full_unstemmed	Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole
title_sort	effector protein cig2 decreases host tolerance of infection by directing constitutive fusion of autophagosomes with the <italic toggle="yes">coxiella</italic>-containing vacuole
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/8bb47c6794e64fadac548e48b9bdf846
work_keys_str_mv	AT larajkohler effectorproteincig2decreaseshosttoleranceofinfectionbydirectingconstitutivefusionofautophagosomeswiththeitalictoggleyescoxiellaitaliccontainingvacuole AT shawnarreed effectorproteincig2decreaseshosttoleranceofinfectionbydirectingconstitutivefusionofautophagosomeswiththeitalictoggleyescoxiellaitaliccontainingvacuole AT shireenasarraf effectorproteincig2decreaseshosttoleranceofinfectionbydirectingconstitutivefusionofautophagosomeswiththeitalictoggleyescoxiellaitaliccontainingvacuole AT daviddarteaga effectorproteincig2decreaseshosttoleranceofinfectionbydirectingconstitutivefusionofautophagosomeswiththeitalictoggleyescoxiellaitaliccontainingvacuole AT hayleyjnewton effectorproteincig2decreaseshosttoleranceofinfectionbydirectingconstitutivefusionofautophagosomeswiththeitalictoggleyescoxiellaitaliccontainingvacuole AT craigrroy effectorproteincig2decreaseshosttoleranceofinfectionbydirectingconstitutivefusionofautophagosomeswiththeitalictoggleyescoxiellaitaliccontainingvacuole
_version_	1718427411797770240

Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the <italic toggle="yes">Coxiella</italic>-Containing Vacuole

Ejemplares similares