Entry and survival of Leishmania amazonensis amastigotes within phagolysosome-like vacuoles that shelter Coxiella burnetii in Chinese hamster ovary cells

Veras, Patrícia Sampaio Tavares; Moulia, Catherine; Dauguet, C.; Tunis, C. T.; Thibon, M; Rabinovitch, M.

doi:10.1128/iai.63.9.3502-3506.1995

Cited by 55 publications

(28 citation statements)

References 30 publications

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“…Coinfection studies also provide information regarding the nutritional character and toxicity of PVs. M. avium, L. amazonensis and T. cruzi efficiently replicate in the Coxiella PV (Veras et al, 1995;Gomes et al, 1999;Andreoli et al, 2006), while M. tuberculosis does not. Interestingly, type IV secretion-deficient Legionella dotA mutants traffic to the Coxiella PV where they survive but fail to replicate (Sauer et al, 2005).…”

Section: Insight From Coinfection Of Cultured Cells With Coxiella Andmentioning

confidence: 99%

“…A common theme of these three pathogens is that their respective nascent phagosomes disconnect from the endocytic cascade soon after infection (Heinzen et al, 1996;Sinai et al, 2000;Roy et al, 2006). In contrast, mature Coxiella PV readily fuse with parasite vacuoles that remain in the endocytic pathway, including those of Mycobacterium avium (de Chastellier et al, 1999;Gomes et al, 1999), Mycobacterium tuberculosis (Gomes et al, 1999), Salmonella enterica (Drecktrah et al, 2007), Leishmania amazonensis (Veras et al, 1995) and Trypanosoma cruzi Fig. 2.…”

Section: Insight From Coinfection Of Cultured Cells With Coxiella Andmentioning

confidence: 99%

“…(Andreoli et al, 2006). The cohabitation of L. amazonensis, T. cruzi and S. enterica with Coxiella is not surprising as these pathogens normally traffic to vacuoles with lysosomal characteristics (Veras et al, 1995;Andreoli et al, 2006;Drecktrah et al, 2007). More striking is the trafficking of M. avium and M. tuberculosis to the Coxiella PV as maturation of their respective vacuoles normally stalls at an early endosomal stage (Clemens and Horwitz, 1995;Sturgill-Koszycki et al, 1996).…”

Section: Insight From Coinfection Of Cultured Cells With Coxiella Andmentioning

confidence: 99%

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Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii

Voth

Heinzen²

2007

Cell Microbiol

11,780

281

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SummaryMost intracellular parasites employ sophisticated mechanisms to direct biogenesis of a vacuolar replicative niche that circumvents default maturation through the endolysosomal cascade. However, this is not the case of the Q fever bacterium, Coxiella burnetii. This hardy, obligate intracellular pathogen has evolved to not only survive, but to thrive, in the harshest of intracellular compartments: the phagolysosome. Following internalization, the nascent Coxiella phagosome ultimately develops into a large and spacious parasitophorous vacuole (PV) that acquires lysosomal characteristics such as acidic pH, acid hydrolases and cationic peptides, defences designed to rid the host of intruders. However, transit of Coxiella to this environment is initially stalled, a process that is apparently modulated by interactions with the autophagic pathway. Coxiella actively participates in biogenesis of its PV by synthesizing proteins that mediate phagosome stalling, autophagic interactions, and development and maintenance of the mature vacuole. Among the potential mechanisms mediating these processes is deployment of a type IV secretion system to deliver effector proteins to the host cytosol. Here we summarize our current understanding of the cellular events that occur during parasitism of host cells by Coxiella.

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Section: Insight From Coinfection Of Cultured Cells With Coxiella Andmentioning

confidence: 99%

Section: Insight From Coinfection Of Cultured Cells With Coxiella Andmentioning

confidence: 99%

Section: Insight From Coinfection Of Cultured Cells With Coxiella Andmentioning

confidence: 99%

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Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii

Voth

Heinzen²

2007

Cell Microbiol

11,780

281

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“…Fusion between lysosomes and nascent phagosomes harbouring viable C. burnetii takes about 4 h, while fusion between lysosomes and phagosomes containing latex beads or inactivated C. burnetii occurs within 30 min (Howe and Mallavia, 2000). C. burnetii PV demonstrate promiscuous homotypic and heterotypic fusion with endolysosomal vacuoles, a process that presumably provides membrane for the expanding PV and nutrients for pathogen replication (Veras et al ., 1994;1995;Howe et al ., 2003). C. burnetii PV further deviate from typical endosomal maturation by interacting with the autophagy pathway to acquire some characteristics of autophagolysosomes (Beron et al ., 2002;Gutierrez et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

Coxiella burnetii inhabits a cholesterol-rich vacuole and influences cellular cholesterol metabolism

2006

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SummaryCoxiella burnetii directs the synthesis of a large parasitophorous vacuole (PV) required for replication. While some lysosomal characteristics of the PV have been described, the origin and composition of the PV membrane is largely undefined. Cholesterol is an essential component of mammalian cell membranes where it plays important regulatory and structural roles. Here we investigated the role of host cholesterol in biogenesis and maintenance of the C. burnetii PV in Vero cells. The C. burnetii PV membrane stained with filipin and was positive for the lipid raft protein flotillin-1, suggesting PV membranes are enriched in cholesterol and contain lipid raft microdomains. C. burnetii infection increased host cell cholesterol content by 1.75-fold with a coincident upregulation of host genes involved in cholesterol metabolism. Treatment with U18666A, lovastatin, or 25-hydroxycholesterol, pharmacological agents that inhibit cholesterol uptake and/or biosynthesis, altered PV morphology and partially inhibited C. burnetii replication. Complete inhibition of C. burnetii PV development and replication was observed when infected cells were treated with imipramine or ketoconazole, inhibitors of cholesterol uptake and biosynthesis respectively. We conclude that C. burnetii infection perturbs host cell cholesterol metabolism and that free access to host cholesterol stores is required for optimal C. burnetii replication.

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“…Interestingly, coinfection studies have shown that PVs formed by L. amazonensis amastigotes can fuse with C. burnetii PVs but not with PVs containing L. major amastigotes, suggesting that the intracellular niches generated by Leishmania mexicana complex parasites and Coxiella may be compositionally rather similar(Real et al 2010;Beare et al 2011;Veras et al 1995;Rabinovitch and Veras 1996;Newton and Roy 2011).Both Coxiella and Leishmania actively participate in the creation of their respective PVsWaller and McConville 2002). To begin to understand how the two distantly related pathogens generate phenotypically similar PVs,…”

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confidence: 99%

Uncovering Coxiella burnetii's Pathogenicity by Elucidating its Metabolism and Host Interactions

Millar¹

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Coxiella burnetii, the etiologic agent of acute Q fever and chronic endocarditis, has a unique biphasic life cycle, which includes a metabolically active intracellular form that occupies a large lysosome-derived acidic vacuole. C. burnetii is the only bacterium known to thrive within such a hostile intracellular niche, and this ability is fundamental to its pathogenicity; however, very little is known about genes that facilitate Coxiella's intracellular growth. This lack of knowledge of Coxiella's basic biology and molecular pathogenesis is a critical barrier to developing more effective therapies.In this study, we aimed to understand both bacterial and host factors that have important roles during C. burnetii infections. Using an evolutionary genomics approach, we identified metabolic pathways that are critical to C. burnetii's ability to grow intracellularly. Among those found, the most promising are fatty acid, biotin, and heme biosyntheses pathways. Coxiella has horizontally acquired extra copies of genes that enhance these processes; when these genes were disrupted, Coxiella's growth was significantly inhibited. Also, by analyzing the host transcriptome, we identified human genes, including microRNA (miRNA) genes that are important during C. burnetii infections. Coxiella induces the expression of multiple anti-apoptotic miRNAs, which likely have a role in inhibiting apoptosis in order to sustain the intracellular replication of the pathogen. The biosynthetic pathways and miRNAs identified in this study are ideal targets for developing more effective therapeutic strategies against Q fever and its chronic and often fatal complications. ii ACKNOWLEDGEMENTS I would like to thank my research advisor Rahul Raghavan of the Biology Department at Portland State University. He has provided continual support but also generous freedom that has allowed me to design aspects and conduct much of this project independently. I would also like to acknowledge Rahul and Tina Schroyer for their assistance in writing my thesis. Their feedback has helped me become a better writer. I want to thank Abraham Moses and Fenil Kacharia for their assistance with conducting all the physical experiments and other lab duties. I also want to thank Todd Smith for taking the time to supplement my learning in bioinformatics. I would also like to thank my thesis committee: Susan Masta and Kenneth Stedman. I appreciate their time and effort reviewing my paper and supporting my research and education.

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Entry and survival of Leishmania amazonensis amastigotes within phagolysosome-like vacuoles that shelter Coxiella burnetii in Chinese hamster ovary cells

Cited by 55 publications

References 30 publications

Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii

Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii

Coxiella burnetii inhabits a cholesterol-rich vacuole and influences cellular cholesterol metabolism

Uncovering Coxiella burnetii's Pathogenicity by Elucidating its Metabolism and Host Interactions

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