General Information:

Id: 2,024
Diseases: Q fever
pathogen-host system
Coxiella burnetii/mammalia
review
Reference: Oyston PC and Davies C(2011) Q fever: the neglected biothreat agent J. Med. Microbiol. 60: 9-21 [PMID: 21030501]

Interaction Information:

Comment Coxiella burnetii is the causative agent of Q fever, a disease with a spectrum of presentations from the mild to fatal, including chronic sequelae.
Formal Description
Interaction-ID: 16087

process

Coxiella burnetii infection

increases_activity of

disease

Q fever, acute

Comment The parasitophorous vacuole (PV) is an acidic environment (pH 4.7-4.8), and the low pH appears to trigger the conversion of SCVs to LCVs.
Formal Description
Interaction-ID: 16092

increases_quantity of

organism

Coxiella burnetii, LCV

Comment C. burnetii can infect a range of cells, including monocytes and macrophages, and cell lines, including macrophages, fibroblast and epithelial cells.
Formal Description
Interaction-ID: 16141

process

Coxiella burnetii infection

increases_activity of

Comment C. burnetii can infect a range of cells, including monocytes and macrophages, and cell lines, including macrophages, fibroblast and epithelial cells.
Formal Description
Interaction-ID: 16142

process

Coxiella burnetii infection

increases_activity of

Comment The uterus and mammary glands are sites of chronic C. burnetii infection in females, and this is associated with abortions in goats and sheep, and infertility in cattle.
Formal Description
Interaction-ID: 16143

process

Coxiella burnetii infection

is localized in

tissue/cell line

mammary gland

during chronic infection
Comment The uterus and mammary glands are sites of chronic C. burnetii infection in females, and this is associated with abortions in goats and sheep, and infertility in cattle.
Formal Description
Interaction-ID: 16144

process

Coxiella burnetii infection

is localized in

tissue/cell line

uterus

during chronic infection
Comment Doxycycline (200 mg daily for 14 days) is the current drug of choice for acute Q fever.
Formal Description
Interaction-ID: 16146

drug/chemical compound

Doxycycline

decreases_activity of

disease

Q fever, acute

Drugbank entries Show/Hide entries for Doxycycline
Comment The alveolar macrophage has been proposed as the primary target.
Formal Description
Interaction-ID: 16149

process

Coxiella burnetii infection

is localized in

tissue/cell line

alveolar macrophage

Comment It has been shown that the replication of phase I and phase II cells is very similar in human monocyte-derived macrophages.
Formal Description
Interaction-ID: 16152

organism

Coxiella burnetii, phase I

increases_activity of

process

Coxiella burnetii replication

in human monocyte-derived macrophages
Comment It has been shown that the replication of phase I and phase II cells is very similar in human monocyte-derived macrophages.
Formal Description
Interaction-ID: 16154

organism

Coxiella burnetii, phase II

increases_activity of

process

Coxiella burnetii replication

in human monocyte-derived macrophages
Comment The parasitophorous vacuole (PV) is an acidic environment (pH 4.7-4.8), and the low pH appears to trigger the conversion of SCVs to LCVs.
Formal Description
Interaction-ID: 16155

decreases_quantity of

organism

Coxiella burnetii, SCV

Comment Similarly to a wide range of Gram-negative pathogens, the LPS is a dominant virulence factor of C. burnetii. LPS does not appear to play a role in survival within the PV (parasitophorous vacuole), as both phase I and II cells were observed within PVs, and even within the same PV of co-infected cells.
Formal Description
Interaction-ID: 16157

organism

Coxiella burnetii, phase I

is localized in

cellular component

C. burnetii containing vacuole, CCV

Comment Similarly to a wide range of Gram-negative pathogens, the LPS is a dominant virulence factor of C. burnetii. LPS does not appear to play a role in survival within the PV (parasitophorous vacuole), as both phase I and II cells were observed within PVs, and even within the same PV of co-infected cells.
Formal Description
Interaction-ID: 16158

organism

Coxiella burnetii, phase II

is localized in

cellular component

C. burnetii containing vacuole, CCV

Comment LPS is a dominant virulence factor of C. burnetii. LPS contributes to the uptake of virulent strains by a Toll-like receptor 4-dependent mechanism.
Formal Description
Interaction-ID: 16160

gene/protein

TLR4

affects_activity of

of C. burnetii into host
Drugbank entries Show/Hide entries for TLR4
Comment The LCV is the intracellular, metabolically active form, which can undergo a division process, with similarities to sporulation, to generate SCVs, the metabolically inactive, highly resistant form released extracellularly to infect new susceptible cells.
Formal Description
Interaction-ID: 16164

organism

Coxiella burnetii, LCV

affects_quantity of

organism

Coxiella burnetii, SCV

Comment Few proteins important for intracellular survival of the pathogen C. burnetii have been identified, including superoxide dismutase, catalase and macrophage infectivity potentiator (CbMip).
Formal Description
Interaction-ID: 16165

gene/protein

mip

increases_activity of

process

pathogen survival

Comment Actin dynamics are often regulated by Rho GTPases, and in HeLa cells the correct formation of the mature C. burnetii vacuole appeared to be dependent upon two such proteins, RhoA and Cdc42.
Formal Description
Interaction-ID: 16215

gene/protein

RHOA

affects_activity of

Drugbank entries Show/Hide entries for RHOA
Comment Actin dynamics are often regulated by Rho GTPases, and in HeLa cells the correct formation of the mature C. burnetii vacuole appeared to be dependent upon two such proteins, RhoA and Cdc42.
Formal Description
Interaction-ID: 16223

gene/protein

CDC42

affects_activity of

Drugbank entries Show/Hide entries for CDC42
Comment Phase I Coxiella burnetii triggers tumour necrosis factor (TNF) synthesis by infected monocytes.
Formal Description
Interaction-ID: 16237

organism

Coxiella burnetii, phase I

increases_quantity of

gene/protein

TNF

in infected monocytes
Drugbank entries Show/Hide entries for TNF
Comment TNF, in conjunction with gamma interferon (IFN-gamma), results in the killing of Coxiella burnetii in THP-1 monocytes.
Formal Description
Interaction-ID: 16238

gene/protein

TNF

decreases_activity of

process

pathogen survival

in THP-1 infected monocytes
Drugbank entries Show/Hide entries for TNF
Comment TNF, in conjunction with gamma interferon (IFN-gamma), results in the killing of Coxiella burnetii in THP-1 monocytes.
Formal Description
Interaction-ID: 16239

gene/protein

IFNG

decreases_activity of

process

pathogen survival

in THP-1 infected monocytes
Drugbank entries Show/Hide entries for IFNG
Comment Although IFN-gamma is key to controlling Q fever, apoptosis is closely controlled by the invading Coxiella to maintain viability of the host cell during the lengthy inhabitation. Infected host cells show decreased caspase activity, induction of a pro-survival transcriptional response, including Akt and Erk 1/2 activation, and decreased release of cytochrome c.
Formal Description
Interaction-ID: 16241

process

Coxiella burnetii infection

decreases_activity of

process

host cell apoptosis

in infected host cells
Comment Although IFN-gamma is key to controlling Q fever, apoptosis is closely controlled by the invading Coxiella to maintain viability of the host cell during the lengthy inhabitation. Infected host cells show decreased caspase activity, induction of a pro-survival transcriptional response, including Akt and Erk 1/2 activation, and decreased release of cytochrome c.
Formal Description
Interaction-ID: 16242

process

Coxiella burnetii infection

increases_activity of

in infected host cells
Comment Although IFN-gamma is key to controlling Q fever, apoptosis is closely controlled by the invading Coxiella to maintain viability of the host cell during the lengthy inhabitation. Infected host cells show decreased caspase activity, induction of a pro-survival transcriptional response, including Akt and Erk 1/2 activation, and decreased release of cytochrome c.
Formal Description
Interaction-ID: 16243

process

Coxiella burnetii infection

increases_activity of

in infected host cells
Comment In addition to controlling apoptosis, Coxiella burnetii modulates autophagy. The autophagy pathway protein Beclin 1 (not Bectin 1) and the anti-apoptotic protein Bcl 2 (not Bcl 1) are both recruited to the membrane of the vacuole surrounding the Coxiella.
Formal Description
Interaction-ID: 16246

gene/protein

BECN1

is localized in

cellular component

C. burnetii containing vacuole, CCV

on the vacuole membrane of infected host cells
Comment In addition to controlling apoptosis, Coxiella burnetii modulates autophagy. The autophagy pathway protein Beclin 1 (not Bectin 1) and the anti-apoptotic protein Bcl 2 (not Bcl 1) are both recruited to the membrane of the vacuole surrounding the Coxiella.
Formal Description
Interaction-ID: 16262

gene/protein

BCL2

is localized in

cellular component

C. burnetii containing vacuole, CCV

on the vacuole membrane of infected host cells
Drugbank entries Show/Hide entries for BCL2
Comment In addition to controlling apoptosis, Coxiella burnetii modulates autophagy. The autophagy pathway protein Beclin 1 (not Bectin 1) and the anti-apoptotic protein Bcl 2 (not Bcl 1) are both recruited to the membrane of the vacuole surrounding the Coxiella.
Formal Description
Interaction-ID: 16263

gene/protein

BECN1

increases_activity of

process

autophagy

Comment In addition to controlling apoptosis, Coxiella burnetii modulates autophagy. The autophagy pathway protein Beclin 1 (not Bectin 1) and the anti-apoptotic protein Bcl 2 (not Bcl 1) are both recruited to the membrane of the vacuole surrounding the Coxiella.
Formal Description
Interaction-ID: 16264

gene/protein

BCL2

decreases_activity of

process

host cell apoptosis

Drugbank entries Show/Hide entries for BCL2
Comment Coxiella burnetii has a unique intracellular lifestyle with two distinct morphological forms, the log-phase large cell variant (LCV) and the stationary-phase small cell variant (SCV). SCVs are metabolically inactive, and show a high degree of resistance to chemical agents and physical conditions, which confers the ability to survive for prolonged periods in the environment.
Formal Description
Interaction-ID: 16400

organism

Coxiella burnetii, SCV

increases_activity of

process

pathogen survival

Comment Coxiella burnetii is the causative agent of Q fever, a disease with a spectrum of presentations from the mild to fatal, including chronic sequelae.
Formal Description
Interaction-ID: 17575

process

Coxiella burnetii infection

increases_activity of

disease

Q fever, chronic

Comment Morphogenesis from SCV to LCV occurs during an initial lag phase with no increase in bacterial number.
Formal Description
Interaction-ID: 35843

organism

Coxiella burnetii, SCV

affects_quantity of

organism

Coxiella burnetii, LCV

during an initial lag phase