General Information:

Id: 3,770
Diseases: Q fever
pathogen-host system
Coxiella burnetii/mammalia
bone marrow-derived macrophages (BMDMs), infected with virulent/avirulent (phase I/phase II) C. burnetii or virulent/avirulent LPS (vLPS/avLPS)
article
Reference: Barry AO et al.(2012) Impaired Stimulation of p38alpha-MAPK/Vps41-HOPS by LPS from Pathogenic Coxiella burnetii Prevents Trafficking to Microbicidal Phagolysosomes Cell Host Microbe 12: 751-763 [PMID: 23245320]

Interaction Information:

Comment In intracellular localization experiments applying virulent/avirulent Coxiella burnetii (vCb/avCb) or the corresponding virulent/avirulent lipopolysaccharides (vLPS/avLPS) to bone marrow-derived macrophages (BMDMs), it was shown that avCb bacteria or avLPS localized in phagolysosomal compartments, which are defined by the presence of LAMP-1, cathepsin D (catD) and RAB7.
Formal Description
Interaction-ID: 36760

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

gene/protein

LAMP1

in BMDMs; infected with avirulent C. burnetii or avirulent LPS
Comment In intracellular localization experiments applying virulent/avirulent Coxiella burnetii (vCb/avCb) or the corresponding virulent/avirulent lipopolysaccharides (vLPS/avLPS) to bone marrow-derived macrophages (BMDMs), it was shown that avCb bacteria or avLPS localized in phagolysosomal compartments, which are defined by the presence of LAMP-1, cathepsin D (catD) and RAB7.
Formal Description
Interaction-ID: 36765

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

gene/protein

RAB7

in BMDMs; infected with avirulent C. burnetii or avirulent LPS
Comment In intracellular localization experiments applying virulent/avirulent Coxiella burnetii (vCb/avCb) or the corresponding virulent/avirulent lipopolysaccharides (vLPS/avLPS) to bone marrow-derived macrophages (BMDMs), it was shown that avCb bacteria or avLPS localized in phagolysosomal compartments, which are defined by the presence of LAMP-1, cathepsin D (catD) and RAB7.
Formal Description
Interaction-ID: 36766

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

gene/protein

CTSD

in BMDMs; infected with avirulent C. burnetii or avirulent LPS
Drugbank entries Show/Hide entries for CTSD
Comment In intracellular localization experiments applying virulent/avirulent Coxiella burnetii (vCb/avCb) or the corresponding virulent/avirulent lipopolysaccharides (vLPS/avLPS) to bone marrow-derived macrophages (BMDMs), it was shown that vCb bacteria or vLPS localized to compartments showing the acquisition of LAMP-1, but were devoid of catD and RAB7.
Formal Description
Interaction-ID: 36768

organism

Coxiella burnetii, phase I

interacts (colocalizes) with

gene/protein

LAMP1

in BMDMs; infected with virulent C. burnetii or virulent LPS
Comment In intracellular localization experiments applying virulent/avirulent Coxiella burnetii (vCb/avCb) or the corresponding virulent/avirulent lipopolysaccharides (vLPS/avLPS) to bone marrow-derived macrophages (BMDMs), it was shown that vCb bacteria or vLPS localized to compartments showing the acquisition of LAMP-1, but were devoid of catD and RAB7.
Formal Description
Interaction-ID: 36769

organism

Coxiella burnetii, phase I

NOT interacts (colocalizes) with

gene/protein

RAB7

in BMDMs; infected with virulent C. burnetii or virulent LPS
Comment In intracellular localization experiments applying virulent/avirulent Coxiella burnetii (vCb/avCb) or the corresponding virulent/avirulent lipopolysaccharides (vLPS/avLPS) to bone marrow-derived macrophages (BMDMs), it was shown that vCb bacteria or vLPS localized to compartments showing the acquisition of LAMP-1, but were devoid of catD and RAB7.
Formal Description
Interaction-ID: 36770

organism

Coxiella burnetii, phase I

NOT interacts (colocalizes) with

gene/protein

CTSD

in BMDMs; infected with virulent C. burnetii or virulent LPS
Drugbank entries Show/Hide entries for CTSD
Comment Analyzing the distribution of the proteins RAB5 and RAB7 on the membranes of vLPS (virulent-LPS)- or avLPS (antivirulent-LPS)-containing compartments it was shown that there is a transient colocalization of avLPS and RAB5 and of vLPS and RAB5 in BMDMs.
Formal Description
Interaction-ID: 36773

organism

Coxiella burnetii, phase I

interacts (colocalizes) with

gene/protein

RAB5

in BMDMs; infected with virulent LPS
Comment Analyzing the distribution of the proteins RAB5 and RAB7 on the membranes of vLPS (virulent-LPS)- or avLPS (antivirulent-LPS)-containing compartments it was shown that there is a transient colocalization of avLPS and RAB5 and of vLPS and RAB5 in BMDMs.
Formal Description
Interaction-ID: 36774

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

gene/protein

RAB5

in BMDMs; infected with avirulent LPS
Comment In an attempt to monitor MAPK activation by C. burnetii avLPS (avirulent) and vLPS (virulent) it was shown that either form of LPS stimulated the ERK1/2 and JNK-signaling pathways in BMDMs within 30 min of treatment.
Formal Description
Interaction-ID: 36791

organism

Coxiella burnetii, phase I

increases_activity of

in BMDMs; infected with virulent LPS
Comment In an attempt to monitor MAPK activation by C. burnetii avLPS (avirulent) and vLPS (virulent) it was shown that either form of LPS stimulated the ERK1/2 and JNK-signaling pathways in BMDMs within 30 min of treatment.
Formal Description
Interaction-ID: 36792

organism

Coxiella burnetii, phase I

increases_activity of

gene/protein

MAPK8

in BMDMs; infected with virulent LPS
Drugbank entries Show/Hide entries for MAPK8
Comment In an attempt to monitor MAPK activation by C. burnetii avLPS (avirulent) and vLPS (virulent) it was shown that either form of LPS stimulated the ERK1/2 and JNK-signaling pathways in BMDMs within 30 min of treatment.
Formal Description
Interaction-ID: 36793

organism

Coxiella burnetii, phase II

increases_activity of

in BMDMs; infected with avirulent LPS
Comment In an attempt to monitor MAPK activation by C. burnetii avLPS (avirulent) and vLPS (virulent) it was shown that either form of LPS stimulated the ERK1/2 and JNK-signaling pathways in BMDMs within 30 min of treatment.
Formal Description
Interaction-ID: 36794

organism

Coxiella burnetii, phase II

increases_activity of

gene/protein

MAPK8

in BMDMs; infected with avirulent LPS
Drugbank entries Show/Hide entries for MAPK8
Comment Within a treatment of 30 min the authors analysed the absence of phosphorylated p38alpha-MAPK in BMDMs challenged with vLPS or vCb (virulent LPS or C. burnetii), in contrast to avLPS-or avCb (avirulent LPS or C. burnetii)-challenged BMDMs, in which phosphorylated p38a-MAPK could be detected. Thus p38alpha-MAPK can be defined as a key host factor differentially engaged during infection with avirulent and virulent strains of C. burnetii.
Formal Description
Interaction-ID: 36795

organism

Coxiella burnetii, phase II

increases_activity of

gene/protein

p38 MAPK

in BMDMs; infected with avirulent LPS or avirulent C. burnetii
Comment Within a treatment of 30 min the authors analysed the absence of phosphorylated p38alpha-MAPK in BMDMs challenged with vLPS or vCb (virulent LPS or C. burnetii), in contrast to avLPS-or avCb (avirulent LPS or C. burnetii)-challenged BMDMs, in which phosphorylated p38a-MAPK could be detected. Thus p38alpha-MAPK can be defined as a key host factor differentially engaged during infection with avirulent and virulent strains of C. burnetii.
Formal Description
Interaction-ID: 36796

organism

Coxiella burnetii, phase I

NOT increases_activity of

gene/protein

p38 MAPK

in BMDMs; infected with virulent LPS or virulent C. burnetii
Comment Within a treatment of 30 min the authors analysed the absence of phosphorylated p38alpha-MAPK in BMDMs challenged with vLPS or vCb (virulent LPS or C. burnetii), in contrast to avLPS-or avCb (avirulent LPS or C. burnetii)-challenged BMDMs, in which phosphorylated p38a-MAPK could be detected. Thus p38alpha-MAPK can be defined as a key host factor differentially engaged during infection with avirulent and virulent strains of C. burnetii.
Formal Description
Interaction-ID: 36797

organism

Coxiella burnetii, phase II

increases_phosphorylation of

gene/protein

p38 MAPK

in BMDMs; infected with avirulent LPS or avirulent C. burnetii
Comment Within a treatment of 30 min the authors analysed the absence of phosphorylated p38alpha-MAPK in BMDMs challenged with vLPS or vCb (virulent LPS or C. burnetii), in contrast to avLPS-or avCb (avirulent LPS or C. burnetii)-challenged BMDMs, in which phosphorylated p38a-MAPK could be detected. Thus p38alpha-MAPK can be defined as a key host factor differentially engaged during infection with avirulent and virulent strains of C. burnetii.
Formal Description
Interaction-ID: 36798

organism

Coxiella burnetii, phase I

NOT increases_phosphorylation of

gene/protein

p38 MAPK

in BMDMs; infected with virulent LPS or virulent C. burnetii
Comment The p38alpha-MAPK upstream activator MKK3/6 has not been induced in BMDMs stimulated with C. burnetii vLPS (virulent), but in BMDMs stimulated with C. burnetii avLPS (avirulent)
Formal Description
Interaction-ID: 36799

gene/protein

MAP2K3

increases_activity of

gene/protein

p38 MAPK

Comment The p38alpha-MAPK upstream activator MKK3/6 has not been induced in BMDMs stimulated with C. burnetii vLPS (virulent), but in BMDMs stimulated with C. burnetii avLPS (avirulent)
Formal Description
Interaction-ID: 36800

gene/protein

MAP2K6

increases_activity of

gene/protein

p38 MAPK

Comment The p38alpha-MAPK upstream activator MKK3/6 has not been induced in BMDMs stimulated with C. burnetii vLPS (virulent), but in BMDMs stimulated with C. burnetii avLPS (avirulent)
Formal Description
Interaction-ID: 36801

organism

Coxiella burnetii, phase I

NOT increases_activity of

gene/protein

MAP2K3

in BMDMs; infected with virulent LPS
Comment The p38alpha-MAPK upstream activator MKK3/6 has not been induced in BMDMs stimulated with C. burnetii vLPS (virulent), but in BMDMs stimulated with C. burnetii avLPS (avirulent)
Formal Description
Interaction-ID: 36802

organism

Coxiella burnetii, phase I

NOT increases_activity of

gene/protein

MAP2K6

in BMDMs; infected with virulent LPS
Comment The p38alpha-MAPK upstream activator MKK3/6 has not been induced in BMDMs stimulated with C. burnetii vLPS (virulent), but in BMDMs stimulated with C. burnetii avLPS (avirulent)
Formal Description
Interaction-ID: 36803

organism

Coxiella burnetii, phase II

increases_activity of

gene/protein

MAP2K3

in BMDMs; infected with avirulent LPS
Comment The p38alpha-MAPK upstream activator MKK3/6 has not been induced in BMDMs stimulated with C. burnetii vLPS (virulent), but in BMDMs stimulated with C. burnetii avLPS (avirulent)
Formal Description
Interaction-ID: 36804

organism

Coxiella burnetii, phase II

increases_activity of

gene/protein

MAP2K6

in BMDMs; infected with avirulent LPS
Comment The p38alpha-MAPK pathway-dependent trafficking of LPSs to lysosomes requires TLR4. TLR4 is required for vLPS (virulent) to inhibit p38a-MAPK phosphorylation.
Formal Description
Interaction-ID: 36806

gene/protein

TLR4

affects_activity of

gene/protein

p38 MAPK

in BMDMs; infected with virulent LPS
Drugbank entries Show/Hide entries for TLR4
Comment The results establish a critical role for p38alpha-MAPK signaling in C. burnetii fate and trafficking to lysosomes. avLPS (avirulent), but not vLPS (virulent), induces p38alpha-MAPK signaling, which drives endolysosomal conversion.
Formal Description
Interaction-ID: 36807

gene/protein

p38 MAPK

increases_activity of

in BMDMs and MEFs; infected with avirulent LPS
Comment The authors analysed the effect of the p38alpha-MAPK activation on the phosphorylation of Vps41 (protein-sorting complex component). avLPS (avirulent) triggered specifically the phosphorylation of Vps41 on serine residues, no effect was observed with vLPS (virulent).
Formal Description
Interaction-ID: 36820

organism

Coxiella burnetii, phase II

increases_activity of

gene/protein

VPS41

in BMDMs; infected with avirulent LPS
Comment The authors analysed the effect of the p38alpha-MAPK activation on the phosphorylation of Vps41 (protein-sorting complex component). avLPS (avirulent) triggered specifically the phosphorylation of Vps41 on serine residues, no effect was observed with vLPS (virulent).
Formal Description
Interaction-ID: 36821

organism

Coxiella burnetii, phase II

increases_phosphorylation of

gene/protein

VPS41

in BMDMs; infected with avirulent LPS
Comment The authors analysed the effect of the p38alpha-MAPK activation on the phosphorylation of Vps41 (protein-sorting complex component). avLPS (avirulent) triggered specifically the phosphorylation of Vps41 on serine residues, no effect was observed with vLPS (virulent).
Formal Description
Interaction-ID: 36822

organism

Coxiella burnetii, phase I

NOT increases_activity of

gene/protein

VPS41

in BMDMs; infected with virulent LPS
Comment The authors analysed the effect of the p38alpha-MAPK activation on the phosphorylation of Vps41 (protein-sorting complex component). avLPS (avirulent) triggered specifically the phosphorylation of Vps41 on serine residues, no effect was observed with vLPS (virulent).
Formal Description
Interaction-ID: 36823

organism

Coxiella burnetii, phase I

NOT increases_phosphorylation of

gene/protein

VPS41

in BMDMs; infected with virulent LPS
Comment Functional analyses revealed that avLPS (avirulent) and avCb (avirulent C. burnetii) colocalized with Vps41 in contrast to vLPS (virulent) and vCb (virulent C. burnetii), which did not colocalize with Vps41.
Formal Description
Interaction-ID: 36824

organism

Coxiella burnetii, phase II

interacts (colocalizes) with

gene/protein

VPS41

in BMDMs; infected with avirulent LPS
Comment Functional analyses revealed that avLPS (avirulent) and avCb (avirulent C. burnetii) colocalized with Vps41 in contrast to vLPS (virulent) and vCb (virulent C. burnetii), which did not colocalize with Vps41.
Formal Description
Interaction-ID: 36825

organism

Coxiella burnetii, phase I

NOT interacts (colocalizes) with

gene/protein

VPS41

in BMDMs; infected with virulent LPS
Comment Inhibition of p38alpha-MAPK blocked the phosphorylation of Vps41 in BMDMs challenged with avLPS (avirulent.
Formal Description
Interaction-ID: 36826

gene/protein

p38 MAPK

increases_activity of

gene/protein

VPS41

in BMDMs; infected with avirulent LPS
Comment Inhibition of p38alpha-MAPK blocked the phosphorylation of Vps41 in BMDMs challenged with avLPS (avirulent.
Formal Description
Interaction-ID: 36827

gene/protein

p38 MAPK

increases_phosphorylation of

gene/protein

VPS41

in BMDMs; infected with avirulent LPS
Comment p38alpha-MAPK coimmunoprecipitated with Vps41, and vice versa, demonstrating their interaction in avLPS (avirulent)-treated BMDMs .
Formal Description
Interaction-ID: 36829

gene/protein

p38 MAPK

interacts (colocalizes) with

gene/protein

VPS41

in BMDMs; infected with avirulent LPS
Comment The phosphorylation of Vps41 by p38alpha-MAPK at serine 796 promotes the trafficking of avirulent C. burnetii bacteria and LPS to lysosomes.
Formal Description
Interaction-ID: 36830

gene/protein

VPS41

increases_activity of

in BMDMs; infected with avirulent LPS
Comment TLR4 is required for the differential stimulation of p38alpha-MAPK. BMDMs challenged with avLPS (avirulent) did not activate p38a-MAPK and failed to induce Vps41 phosphorylation in TLR4-deficient macrophages.
Formal Description
Interaction-ID: 36839

organism

Coxiella burnetii, phase II

increases_activity of

gene/protein

TLR4

in BMDMs; infected with avirulent LPS
Drugbank entries Show/Hide entries for TLR4
Comment TLR4 is required for the differential stimulation of p38alpha-MAPK. TLR4 is necessary for the inhibition of p38a-MAPK phosphorylation when cells are stimulated with vLPS, showing that vLPS (virulent) acts as an antagonist of TLR4.
Formal Description
Interaction-ID: 36840

organism

Coxiella burnetii, phase I

decreases_activity of

gene/protein

TLR4

in BMDMs; infected with virulent LPS
Drugbank entries Show/Hide entries for TLR4
Comment In an attempt to monitor MAPK activation by C. burnetii avLPS (avirulent) and vLPS (virulent) it was shown that either form of LPS stimulated the ERK1/2 and JNK-signaling pathways in BMDMs within 30 min of treatment.
Formal Description
Interaction-ID: 36899

organism

Coxiella burnetii, phase I

increases_phosphorylation of

gene/protein

MAPK8

in BMDMs; infected with virulent LPS
Drugbank entries Show/Hide entries for MAPK8
Comment In an attempt to monitor MAPK activation by C. burnetii avLPS (avirulent) and vLPS (virulent) it was shown that either form of LPS stimulated the ERK1/2 and JNK-signaling pathways in BMDMs within 30 min of treatment.
Formal Description
Interaction-ID: 36901

organism

Coxiella burnetii, phase II

increases_phosphorylation of

gene/protein

MAPK8

in BMDMs; infected with avirulent LPS
Drugbank entries Show/Hide entries for MAPK8
Comment The results establish a critical role for p38alpha-MAPK signaling in C. burnetii fate and trafficking to lysosomes. avLPS (avirulent), but not vLPS (virulent), induces p38alpha-MAPK signaling, which drives endolysosomal conversion.
Formal Description
Interaction-ID: 38611

gene/protein

p38 MAPK

NOT increases_activity of

in BMDMs and MEFs; infected with virulent LPS