Hijacking and Use of Host Kinases by Chlamydiae

Chlamydia species are causative agents of sexually transmitted infections, blinding trachoma, and animal infections with zoonotic potential. Being an obligate intracellular pathogen, Chlamydia relies on the host cell for its survival and development, subverting various host cell processes throughout the infection cycle. A key subset of host proteins utilized by Chlamydia include an assortment of host kinase signaling networks which are vital for many chlamydial processes including entry, nutrient acquisition, and suppression of host cell apoptosis. In this review, we summarize the recent advancements in our understanding of host kinase subversion by Chlamydia.

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Coxiella burnetii Inhibits Activation of Host Cell Apoptosis through a Mechanism That Involves Preventing Cytochrome c Release from Mitochondria

Infection and Immunity ◽

10.1128/iai.00863-07 ◽

2007 ◽

Vol 75 (11) ◽

pp. 5282-5289 ◽

Cited By ~ 65

Author(s):

Anja Lührmann ◽

Craig R. Roy

Keyword(s):

Cell Death ◽

Host Cell ◽

Coxiella Burnetii ◽

Mammalian Cells ◽

Q Fever ◽

Host Cells ◽

Intracellular Pathogen ◽

Obligate Intracellular ◽

Cell Death Pathway ◽

Obligate Intracellular Pathogen

ABSTRACT Coxiella burnetii is an obligate intracellular pathogen and the etiological agent of the human disease Q fever. C. burnetii infects mammalian cells and then remodels the membrane-bound compartment in which it resides into a unique lysosome-derived organelle that supports bacterial multiplication. To gain insight into the mechanisms by which C. burnetii is able to multiply intracellularly, we examined the ability of host cells to respond to signals that normally induce apoptosis. Our data show that mammalian cells infected with C. burnetii are resistant to apoptosis induced by staurosporine and UV light. C. burnetii infection prevented caspase 3/7 activation and limited fragmentation of the host cell nucleus in response to agonists that induce apoptosis. Inhibition of bacterial protein synthesis reduced the antiapoptotic effect that C. burnetii exerted on infected host cells. Inhibition of apoptosis in C. burnetii-infected cells did not correlate with the degradation of proapoptotic BH3-only proteins involved in activation of the intrinsic cell death pathway; however, cytochrome c release from mitochondria was diminished in cells infected with C. burnetii upon induction of apoptosis. These data indicate that C. burnetii can interfere with the intrinsic cell death pathway during infection by producing proteins that either directly or indirectly prevent release of cytochrome c from mitochondria. It is likely that inhibition of apoptosis by C. burnetii represents an important virulence property that allows this obligate intracellular pathogen to maintain host cell viability despite inducing stress that would normally activate the intrinsic death pathway.

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Toxoplasma gondii Development of Its Replicative Niche: in Its Host Cell and Beyond

Eukaryotic Cell ◽

10.1128/ec.00081-14 ◽

2014 ◽

Vol 13 (8) ◽

pp. 965-976 ◽

Cited By ~ 32

Author(s):

Ira J. Blader ◽

Anita A. Koshy

Keyword(s):

Toxoplasma Gondii ◽

Host Cell ◽

Host Cells ◽

Content Type ◽

Obligate Intracellular ◽

Cellular Processes ◽

High Prevalence ◽

Life Threatening ◽

Cell Processes ◽

Cellular Pathways

ABSTRACTIntracellular pathogens can replicate efficiently only after they manipulate and modify their host cells to create an environment conducive to replication. While diverse cellular pathways are targeted by different pathogens, metabolism, membrane and cytoskeletal architecture formation, and cell death are the three primary cellular processes that are modified by infections.Toxoplasma gondiiis an obligate intracellular protozoan that infects ∼30% of the world's population and causes severe and life-threatening disease in developing fetuses, in immune-comprised patients, and in certain otherwise healthy individuals who are primarily found in South America. The high prevalence ofToxoplasmain humans is in large part a result of its ability to modulate these three host cell processes. Here, we highlight recent work defining the mechanisms by whichToxoplasmainteracts with these processes. In addition, we hypothesize why some processes are modified not only in the infected host cell but also in neighboring uninfected cells.

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A Chemical Mutagenesis Approach to Identify Virulence Determinants in the Obligate Intracellular Pathogen Chlamydia trachomatis

Host-Bacteria Interactions - Methods in Molecular Biology ◽

10.1007/978-1-4939-1261-2_20 ◽

2014 ◽

pp. 347-358 ◽

Cited By ~ 5

Author(s):

Bidong Nguyen ◽

Raphael Valdivia

Keyword(s):

Chlamydia Trachomatis ◽

Chemical Mutagenesis ◽

Intracellular Pathogen ◽

Virulence Determinants ◽

Obligate Intracellular ◽

Obligate Intracellular Pathogen

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Invasion of Toxoplasma gondii occurs by active penetration of the host cell

Journal of Cell Science ◽

10.1242/jcs.108.6.2457 ◽

1995 ◽

Vol 108 (6) ◽

pp. 2457-2464 ◽

Cited By ~ 4

Author(s):

J.H. Morisaki ◽

J.E. Heuser ◽

L.D. Sibley

Keyword(s):

Toxoplasma Gondii ◽

Host Cell ◽

Tyrosine Phosphorylation ◽

Host Cells ◽

The Novel ◽

Host Proteins ◽

Host Cell Membrane ◽

Membrane Ruffling ◽

Obligate Intracellular ◽

Obligate Intracellular Parasite

Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of vertebrate cells including macrophages. We have used a combination of video microscopy and fluorescence localization to examine the entry of Toxoplasma into macrophages and nonphagocytic host cells. Toxoplasma actively invaded host cells without inducing host cell membrane ruffling, actin microfilament reorganization, or tyrosine phosphorylation of host proteins. Invasion occurred rapidly and within 25–40 seconds the parasite penetrated into a tight-fitting vacuole formed by invagination of the plasma membrane. In contrast, during phagocytosis of Toxoplasma, extensive membrane ruffling captured the parasite in a loose-fitting phagosome that formed over a period of 2–4 minutes. Phagocytosis involved both reorganization of the host cytoskeleton and tyrosine phosphorylation of host proteins. In some cases, parasites that were first internalized by phagocytosis, were able to escape from the phagosome by a process analogous to invasion. These studies reveal that active penetration of the host cell by Toxoplasma is fundamentally different from phagocytosis or induced endocytic uptake. The novel ability to penetrate the host cell likely contributes to the capability of Toxoplasma-containing vacuoles to avoid endocytic processing.

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