General Information:

Id: 3,573
Diseases: Q fever
pathogen-host system
Coxiella burnetii/mammalia
review
Reference: Mertens K and Samuel JE(2012) Defense Mechanisms Against Oxidative Stress in Coxiella burnetii: Adaptation to a Unique Intracellular Niche Adv. Exp. Med. Biol. 984: 39-63 [PMID: 22711626]

Interaction Information:

Comment It has been shown that the suppression of ROS production in polymorphonuclear monocytes (PMNs) or macrophages depends on the secretion of an acid phosphatase (ACP, CBU0335.
Formal Description
Interaction-ID: 33441

gene/protein

CBU_0335

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment It has been shown that pretreatment of PMNs (polymorphonuclear monocytes) with C. burnetii ACP (acid phosphatase) followed by phorbol-12-myristate-13-acetate (PMA) stimulation prevents Phox assembly and that ACP acts as agonist to extracellular signals.
Formal Description
Interaction-ID: 33443

gene/protein

CBU_0335

decreases_quantity of

complex/PPI

NADPH oxidase complex

in polymorphonuclear monocytes (PMNs)
Comment Within the environment of the PV (parasitophorous vacuole), C. burnetii is exposed to varying levels of ROS and RNS, which represent the primary defense mechanism of the host cell against this invading microorganism. The following factors of C. burnetii that can modulate sensitivity and expression of the toxic radicals are superoxide anion converting enzymes FeSOD and Cu-ZnSOD (CBU1708 and CBU1822), catalase (CBU0281), and a secreted ACP (CBU0335).
Formal Description
Interaction-ID: 33446

gene/protein

sodB

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Within the environment of the PV (parasitophorous vacuole), C. burnetii is exposed to varying levels of ROS and RNS, which represent the primary defense mechanism of the host cell against this invading microorganism. The following factors of C. burnetii that can modulate sensitivity and expression of the toxic radicals are superoxide anion converting enzymes FeSOD and Cu-ZnSOD (CBU1708 and CBU1822), catalase (CBU0281), and a secreted ACP (CBU0335).
Formal Description
Interaction-ID: 33448

gene/protein

sodC

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Within the environment of the PV (parasitophorous vacuole), C. burnetii is exposed to varying levels of ROS and RNS, which represent the primary defense mechanism of the host cell against this invading microorganism. The following factors of C. burnetii that can modulate sensitivity and expression of the toxic radicals are superoxide anion converting enzymes FeSOD and Cu-ZnSOD (CBU1708 and CBU1822), catalase (CBU0281 (CBU_0282a)), and a secreted ACP (CBU0335).
Formal Description
Interaction-ID: 33449

gene/protein

CBU_0282a

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Low molecular weight thiols are one class of small proteins, which promote degradation of ROS and RNS and mediate the repair of oxidative and nitrosative modified proteins. One example is the small peptide glutathione, which reduces disulfide often in conjunction with glutaredoxin. The corresponding C. burnetii genes are the glutamate-cysteine ligase (CBU1874) and gshB (CBU1875) and the corresponding glutaredoxin (grxC, CBU1520)
Formal Description
Interaction-ID: 33450

gene/protein

CBU_1874

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Low molecular weight thiols are one class of small proteins, which promote degradation of ROS and RNS and mediate the repair of oxidative and nitrosative modified proteins. One example is the small peptide glutathione, which reduces disulfide often in conjunction with glutaredoxin. The corresponding C. burnetii genes are the glutamate-cysteine ligase (CBU1874) and gshB (CBU1875) and the corresponding glutaredoxin (grxC, CBU1520)
Formal Description
Interaction-ID: 33451

gene/protein

CBU_1874

decreases_quantity of

drug/chemical compound

Reactive nitrogen species

Comment Low molecular weight thiols are one class of small proteins, which promote degradation of ROS and RNS and mediate the repair of oxidative and nitrosative modified proteins. One example is the small peptide glutathione, which reduces disulfide often in conjunction with glutaredoxin. The corresponding C. burnetii genes are the glutamate-cysteine ligase (CBU1874) and gshB (CBU1875) and the corresponding glutaredoxin (grxC, CBU1520)
Formal Description
Interaction-ID: 33452

gene/protein

gshB

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Drugbank entries Show/Hide entries for gshB
Comment Low molecular weight thiols are one class of small proteins, which promote degradation of ROS and RNS and mediate the repair of oxidative and nitrosative modified proteins. One example is the small peptide glutathione, which reduces disulfide often in conjunction with glutaredoxin. The corresponding C. burnetii genes are the glutamate-cysteine ligase (CBU1874) and gshB (CBU1875) and the corresponding glutaredoxin (grxC, CBU1520)
Formal Description
Interaction-ID: 33453

gene/protein

gshB

decreases_quantity of

drug/chemical compound

Reactive nitrogen species

Drugbank entries Show/Hide entries for gshB
Comment Low molecular weight thiols are one class of small proteins, which promote degradation of ROS and RNS and mediate the repair of oxidative and nitrosative modified proteins. One example is the small peptide glutathione, which reduces disulfide often in conjunction with glutaredoxin. The corresponding C. burnetii genes are the glutamate-cysteine ligase (CBU1874) and gshB (CBU1875) and the corresponding glutaredoxin (grxC, CBU1520)
Formal Description
Interaction-ID: 33454

gene/protein

grxC

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Low molecular weight thiols are one class of small proteins, which promote degradation of ROS and RNS and mediate the repair of oxidative and nitrosative modified proteins. One example is the small peptide glutathione, which reduces disulfide often in conjunction with glutaredoxin. The corresponding C. burnetii genes are the glutamate-cysteine ligase (CBU1874) and gshB (CBU1875) and the corresponding glutaredoxin (grxC, CBU1520)
Formal Description
Interaction-ID: 33455

gene/protein

grxC

decreases_quantity of

drug/chemical compound

Reactive nitrogen species

Comment Inhibition of bacterial replication in the presence of iron chelators suggested an absolute requirement for iron and led to the assumption that C. burnetii , similar to L. Pneumophila, regulates iron assimilation via the Fur regulon. The Fur-regulon in C. burnetii consists of CBU1301 and only two Fur-regulated genes, FeoB (CBU1766) and Frg1 (CBU0970)
Formal Description
Interaction-ID: 33456

gene/protein

fur

affects_activity of

Comment Inhibition of bacterial replication in the presence of iron chelators suggested an absolute requirement for iron and led to the assumption that C. burnetii , similar to L. Pneumophila, regulates iron assimilation via the Fur regulon. The Fur-regulon in C. burnetii consists of CBU1301 and only two Fur-regulated genes, FeoB (CBU1766) and Frg1 (CBU0970)
Formal Description
Interaction-ID: 33457

gene/protein

feoB

affects_activity of

Comment Inhibition of bacterial replication in the presence of iron chelators suggested an absolute requirement for iron and led to the assumption that C. burnetii , similar to L. Pneumophila, regulates iron assimilation via the Fur regulon. The Fur-regulon in C. burnetii consists of CBU1301 and only two Fur-regulated genes, FeoB (CBU1766) and Frg1 (CBU0970)
Formal Description
Interaction-ID: 33458

gene/protein

frg1

affects_activity of

Comment Phagocytic cells, known as mediators of the innate immune response, carry two specialized and inducible systems for production of ROS and RNS; the NADPH phagocyte oxidase (Phox) and inducible nitric oxide synthase (iNOS).
Formal Description
Interaction-ID: 33776

complex/PPI

NADPH oxidase complex

increases_quantity of

drug/chemical compound

Reactive oxygen species

in phagocytes
Comment Phagocytic cells, known as mediators of the innate immune response, carry two specialized and inducible systems for production of ROS and RNS; the NADPH phagocyte oxidase (Phox) and inducible nitric oxide synthase (iNOS).
Formal Description
Interaction-ID: 33777

gene/protein

NOS2

increases_quantity of

drug/chemical compound

Reactive nitrogen species

in phagocytes
Drugbank entries Show/Hide entries for NOS2
Comment Experiments in animal models with defects in either Phox or iNOS or both emphasize the importance of these effectors of the innate immune response.
Formal Description
Interaction-ID: 33778

complex/PPI

NADPH oxidase complex

increases_activity of

Comment Experiments in animal models with defects in either Phox or iNOS or both emphasize the importance of these effectors of the innate immune response.
Formal Description
Interaction-ID: 33779

gene/protein

NOS2

increases_activity of

Drugbank entries Show/Hide entries for NOS2
Comment It has been shown that activity of iNOS is regulated by de novo synthesis upon induction by pro-inflammatory cytokines like IFN-gamma, TNF-alpha or TLR ligands (LPS).
Formal Description
Interaction-ID: 33780

gene/protein

IFNG

increases_quantity of

gene/protein

NOS2

Drugbank entries Show/Hide entries for IFNG or NOS2
Comment It has been shown that activity of iNOS is regulated by de novo synthesis upon induction by pro-inflammatory cytokines like IFN-gamma, TNF-alpha or TLR ligands (LPS).
Formal Description
Interaction-ID: 33781

gene/protein

TNF

increases_quantity of

gene/protein

NOS2

Drugbank entries Show/Hide entries for TNF or NOS2
Comment C. burnetii encodes, like L. pneumophila, two peroxide scavenging alkyl hydoperoxide systems, AhpC1 (CBU1706) and AhpC2D (CBU1477/1478). In L. pneumophila AhpCs are the primary peroxide scavengers.
Formal Description
Interaction-ID: 33825

gene/protein

ahpC1

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment C. burnetii encodes, like L. pneumophila, two peroxide scavenging alkyl hydoperoxide systems, AhpC1 (CBU1706) and AhpC2D (CBU1477/1478). In L. pneumophila AhpCs are the primary peroxide scavengers.
Formal Description
Interaction-ID: 33826

gene/protein

ahpC2

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment C. burnetii encodes, like L. pneumophila, two peroxide scavenging alkyl hydoperoxide systems, AhpC1 (CBU1706) and AhpC2D (CBU1477/1478). In L. pneumophila AhpCs are the primary peroxide scavengers.
Formal Description
Interaction-ID: 33827

gene/protein

ahpD

decreases_quantity of

drug/chemical compound

Reactive oxygen species

Comment Due to its accelerating side effect on ROS toxicity, iron assimilation is tightly regulated in bacteria by the small dimeric protein Fur.
Formal Description
Interaction-ID: 33828

affects_quantity of

drug/chemical compound

Reactive oxygen species

Comment Despite the close relation to L. pneumophila, oxyR in C. burnetii seems to be involved in the oxidative stress induced expression of ahpC2.
Formal Description
Interaction-ID: 33829

gene/protein

oxyR

increases_expression of

gene/protein

ahpC2

Drugbank entries Show/Hide entries for oxyR
Comment Within the harsh environment of the PV (parasitophorous vacuole), C. burnetii is constantly exposed to potentially DNA damaging agents generated by the host. Oxidative attack of the DNA by ROS and RNS can cause DNA damage.
Formal Description
Interaction-ID: 33830

drug/chemical compound

Reactive oxygen species

increases_activity of

Comment Within the harsh environment of the PV (parasitophorous vacuole), C. burnetii is constantly exposed to potentially DNA damaging agents generated by the host. Oxidative attack of the DNA by ROS and RNS can cause DNA damage.
Formal Description
Interaction-ID: 33831

drug/chemical compound

Reactive nitrogen species

increases_activity of

Comment The following C. burnetii genes seems to be involved in base excision repair: MutT (CBU0148) 7,8-dihydro-8-oxoguanine-triphosphatase, MutY (CBU_0940) A/G-specific adenine glycosylase and nth endonuclease III. These genes represent a complete GO (8-oxo-7, 8-dihydroguanine (8-oxoG)) system.
Formal Description
Interaction-ID: 33832

gene/protein

mutT

increases_activity of

Drugbank entries Show/Hide entries for mutT
Comment The following C. burnetii genes seems to be involved in base excision repair: MutT (CBU0148) 7,8-dihydro-8-oxoguanine-triphosphatase, MutY (CBU_0940) A/G-specific adenine glycosylase and nth endonuclease III. These genes represent a complete GO (8-oxo-7, 8-dihydroguanine (8-oxoG)) system.
Formal Description
Interaction-ID: 33833

gene/protein

mutY

increases_activity of

Drugbank entries Show/Hide entries for mutY
Comment The following C. burnetii genes seems to be involved in base excision repair: MutT (CBU0148) 7,8-dihydro-8-oxoguanine-triphosphatase, MutY (CBU_0940) A/G-specific adenine glycosylase and nth endonuclease III. These genes represent a complete GO (8-oxo-7, 8-dihydroguanine (8-oxoG)) system.
Formal Description
Interaction-ID: 33834

gene/protein

nth

increases_activity of

Comment The genes tagA (CBU0383) and mpg (CBU0930) are annotated for C. burnetii and might mediate protection against RNS generated DNA damage.
Formal Description
Interaction-ID: 33835

gene/protein

tag

increases_activity of

Drugbank entries Show/Hide entries for tag
Comment The genes tagA (CBU0383) and mpg (CBU0930) are annotated for C. burnetii and might mediate protection against RNS generated DNA damage.
Formal Description
Interaction-ID: 33836

gene/protein

mpg

increases_activity of

Comment The uvr-system is described as part of the nucleotide excision repair. The uvrABC (CBU0274, CBU0518, CBU1185) and uvrD (CBU2054) genes are annotated for C. burnetii and there are indications that the uvr system might contribute to DNA repair under oxidative stress.
Formal Description
Interaction-ID: 33837

gene/protein

uvrA

increases_activity of

Comment The uvr-system is described as part of the nucleotide excision repair. The uvrABC (CBU0274, CBU0518, CBU1185) and uvrD (CBU2054) genes are annotated for C. burnetii and there are indications that the uvr system might contribute to DNA repair under oxidative stress.
Formal Description
Interaction-ID: 33838

gene/protein

uvrB

increases_activity of

Comment The uvr-system is described as part of the nucleotide excision repair. The uvrABC (CBU0274, CBU0518, CBU1185) and uvrD (CBU2054) genes are annotated for C. burnetii and there are indications that the uvr system might contribute to DNA repair under oxidative stress.
Formal Description
Interaction-ID: 33839

gene/protein

uvrC

increases_activity of

Comment The uvr-system is described as part of the nucleotide excision repair. The uvrABC (CBU0274, CBU0518, CBU1185) and uvrD (CBU2054) genes are annotated for C. burnetii and there are indications that the uvr system might contribute to DNA repair under oxidative stress.
Formal Description
Interaction-ID: 33840

gene/protein

uvrD

increases_activity of

Comment The uvr-system is described as part of the nucleotide excision repair. The uvrABC (CBU0274, CBU0518, CBU1185) and uvrD (CBU2054) genes are annotated for C. burnetii and there are indications that the uvr system might contribute to DNA repair under oxidative stres.
Formal Description
Interaction-ID: 33841
Comment The genes tagA (CBU0383) and mpg (CBU0930) are annotated for C. burnetii and might mediate protection against RNS generated DNA damage.
Formal Description
Interaction-ID: 33842
Comment The AddAB complex (CBU1229 and CBU1230) is a functional homolog to recBCD of E. coli. This complex is inducible under oxidative stress and mediates DNA repair via homologous recombination.
Formal Description
Interaction-ID: 33843

gene/protein

CBU_1229

increases_activity of

Comment The AddAB complex (CBU1229 and CBU1230) is a functional homolog to recBCD of E. coli. This complex is inducible under oxidative stress and mediates DNA repair via homologous recombination.
Formal Description
Interaction-ID: 33844

gene/protein

CBU_1230

increases_activity of

Comment The AddAB complex (CBU1229 and CBU1230) is a functional homolog to recBCD of E. coli. This complex is inducible under oxidative stress and mediates DNA repair via homologous recombination.
Formal Description
Interaction-ID: 33845
Comment Within the environment of the PV (parasitophorous vacuole), C. burnetii is exposed to varying levels of ROS and RNS, which represent the primary defense mechanism of the host cell against this invading microorganism.
Formal Description
Interaction-ID: 33846

drug/chemical compound

Reactive oxygen species

increases_activity of

Comment Within the environment of the PV (parasitophorous vacuole), C. burnetii is exposed to varying levels of ROS and RNS, which represent the primary defense mechanism of the host cell against this invading microorganism.
Formal Description
Interaction-ID: 33847

drug/chemical compound

Reactive nitrogen species

increases_activity of

Comment C. burnetii employs several strategies to evade oxidative stress: delaying phagolysosome fusion and inhibiting cellular NADPH oxidase are features attributed to the host side. On the bacterial side, the maintaining of genome stability is managed by a low iron environment, the expression of a minimal and likely crucial set of DNA repair genes and the detoxification of the PV by ROS and RNS degrading enzymes.
Formal Description
Interaction-ID: 33849

increases_activity of

process

pathogen survival

Comment C. burnetii employs several strategies to evade oxidative stress: delaying phagolysosome fusion and inhibiting cellular NADPH oxidase are features attributed to the host side. On the bacterial side, the maintaining of genome stability is managed by a low iron environment, the expression of a minimal and likely crucial set of DNA repair genes and the detoxification of the PV by ROS and RNS degrading enzymes.
Formal Description
Interaction-ID: 33850

increases_activity of

process

pathogen survival