Biogenesis of the lysosome-derived vacuole containing Coxiella burnetii

Kohler, Lara J.; Roy, Craig R.

doi:10.1016/j.micinf.2015.08.006

Cited by 45 publications

(41 citation statements)

References 45 publications

(65 reference statements)

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“…Although levels of lipidated LC3 (LC3-II) increase during Coxiella infection [56,60,67], the overall rate of autophagic flux does not increase as evidenced by the absence of p62 turnover [60,67]. As the CCV expands, endogenous LC3 continues to accumulate in the vacuole lumen, but not the limiting membrane, suggesting constitutive fusion between the CCV and autophagosomes delivering LC3-labeled cargo [60,71]. CCV fusion with autophagosomes is presumed to assist Coxiella by providing membrane for vacuole expansion and nutrients for review Larson [67].…”

Section: Making a Home In Host Cellsmentioning

confidence: 99%

“…Inhibition of autophagy with 3-methyladenine reduces vacuole expansion and pathogen growth whereas the opposite occurs with induction of autophagy by host cell starvation or treatment with the mTOR inhibitor, rapamycin [68,70]. Others have shown siRNA knockdown of essential autophagy proteins results in multiple CCV without negatively impacting Coxiella replication, and that a Coxiella mutant in the effector gene cbu0021 (cvpB, cig2) (discussed in the 'The hard part: effector function' section) replicates normally in an LC3-negative CCV [60,71].…”

Section: Making a Home In Host Cellsmentioning

confidence: 99%

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Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

et al. 2016

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Invasion of macrophages and replication within an acidic and degradative phagolysosomelike vacuole are essential for disease pathogenesis by Coxiella burnetii, the bacterial agent of human Q fever. Previous experimental constraints imposed by the obligate intracellular nature of Coxiella limited knowledge of pathogen strategies that promote infection. Fortunately, new genetic tools facilitated by axenic culture now allow allelic exchange and transposon mutagenesis approaches for virulence gene discovery. Phenotypic screens have illuminated the critical importance of Coxiella's type 4B secretion system in host cell subversion and discovered genes encoding translocated effector proteins that manipulate critical infection events. Here, we highlight the cellular microbiology and genetics of Coxiella and how recent technical advances now make Coxiella a model organism to study macrophage parasitism.

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Section: Making a Home In Host Cellsmentioning

confidence: 99%

Section: Making a Home In Host Cellsmentioning

confidence: 99%

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

et al. 2016

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“…SNAREs such as VAMP7 and Syntaxin-17 play a key role in this process, mediating the fusion events that lead to the biogenesis of large CCVs that occupy the majority of the host cell cytoplasm (5,6). Mature CCVs are dynamic acidic compartments (pH 4.8), containing active hydrolases, which Coxiella is able to resist, and are positive for markers of late endosomes, lysosomes, and autophagosomes such as vATPase, LAMP1, CathepsinD, CD63, and microtubule-associated protein 1A/1B-light chain 3 (LC3) (7). Many efforts are being focused on the identification and characterization of the Coxiella effectors involved in CCV biogenesis, as well as in the identification of the host cell trafficking pathways hijacked by this microbe.…”

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confidence: 99%

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

Martínez

Allombert

Cantet

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

129

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The Q fever bacterium Coxiella burnetii replicates inside host cells within a large Coxiella-containing vacuole (CCV) whose biogenesis relies on the Dot/Icm-dependent secretion of bacterial effectors. Several membrane trafficking pathways contribute membranes, proteins, and lipids for CCV biogenesis. These include the endocytic and autophagy pathways, which are characterized by phosphatidylinositol 3-phosphate [PI(3)P]-positive membranes. Here we show that the C. burnetii secreted effector Coxiella vacuolar protein B (CvpB) binds PI(3)P and phosphatidylserine (PS) on CCVs and early endosomal compartments and perturbs the activity of the phosphatidylinositol 5-kinase PIKfyve to manipulate PI(3)P metabolism. CvpB association to early endosome triggers vacuolation and clustering, leading to the channeling of large PI(3)P-positive membranes to CCVs for vacuole expansion. At CCVs, CvpB binding to early endosome-and autophagy-derived PI(3)P and the concomitant inhibition of PIKfyve favor the association of the autophagosomal machinery to CCVs for optimal homotypic fusion of the Coxiella-containing compartments. The importance of manipulating PI(3)P metabolism is highlighted by mutations in cvpB resulting in a multivacuolar phenotype, rescuable by gene complementation, indicative of a defect in CCV biogenesis. Using the insect model Galleria mellonella, we demonstrate the in vivo relevance of defective CCV biogenesis by highlighting an attenuated virulence phenotype associated with cvpB mutations.Coxiella burnetii | host-pathogen interactions | phosphoinositides

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“…For example, bacteria may respond to an environmental cue by transcribing virulence genes that enable them to colonize a host and potentially cause disease (Ribet and Cossart ). Furthermore, the type II and IV bacterial secretion systems were also enriched within coral ecosphere metagenomes and these systems are typically used by bacteria to colonize surfaces, transport and secrete molecules, induce endocytosis within the host cell, acquire virulence genes, and disrupt host cell defenses (Kohler and Roy ; Green and Mecsas ). The enrichment of secretion systems near corals suggests that these infection strategies may be used by putative pathogens as well as symbionts residing within the ecosphere microbial community to colonize the coral host.…”

Section: Discussionmentioning

confidence: 99%

The coral ecosphere: A unique coral reef habitat that fosters coral–microbial interactions

Weber

González‐Díaz

Armenteros

et al. 2019

Limnology & Oceanography

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Scleractinian corals are bathed in a sea of planktonic and particle‐associated microorganisms. The metabolic products of corals influence the growth and composition of microorganisms, but interactions between corals and seawater microorganisms are underexplored. We conducted a field‐based survey to compare the biomass, diversity, composition, and functional capacity of microorganisms in small‐volume seawater samples collected adjacent to five coral species with seawater collected > 1 m away from the reef substrate on the same reefs. Seawater collected close to corals generally harbored copiotrophic‐type bacteria and its bacterial and archaeal composition was influenced by coral species as well as the local reef environment. Trends in picoplankton abundances were variable and either increased or decreased away from coral colonies based on coral species and picoplankton functional group. Genes characteristic of surface‐attached and potentially virulent microbial lifestyles were enriched in near‐coral seawater compared to reef seawater. There was a prominent association between the coral Porites astreoides and the coral symbiont Endozoicomonas, suggesting recruitment and/or shedding of these cells into the surrounding seawater. This evidence extends our understanding of potential species‐specific and reef site‐influenced microbial interactions that occur between corals and microorganisms within this near‐coral seawater environment that we propose to call the “coral ecosphere.” Microbial interactions that occur within the coral ecosphere could influence recruitment of coral‐associated microorganisms and facilitate the transfer of coral metabolites into the microbial food web, thus fostering reef biogeochemical cycling and a linkage between corals and the water column.

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Biogenesis of the lysosome-derived vacuole containing Coxiella burnetii

Cited by 45 publications

References 45 publications

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development

The coral ecosphere: A unique coral reef habitat that fosters coral–microbial interactions

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