BRENDA - Enzyme Database

Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis

Dunn, M.F.; Ramirez-Trujillo, J.A.; Hernandez-Lucas, I.; Microbiology 155, 3166-3175 (2009)

Data extracted from this reference:

Activating Compound
EC Number
Activating Compound
Commentary
Organism
Structure
4.1.3.1
additional information
high enzymic activity of ICL in strains isolated from diabetic patients suffering from vulvovaginal candidiasis. Specific activation of ICL1 when the pathogen is exposed to neutrophils or macrophages
Candida albicans
4.1.3.1
additional information
ICL activity increases in pellicles in synthetic media as a consequence of fatty acid degradation as well as under microaerophilic growth conditions
Mycobacterium tuberculosis
Application
EC Number
Application
Commentary
Organism
4.1.3.1
additional information
constitutive enzymic activity can be used to identify Yersinia pestis in humans, animals, water, soil and food
Yersinia pestis
Engineering
EC Number
Amino acid exchange
Commentary
Organism
2.3.3.9
D631N
no activity
Escherichia coli
2.3.3.9
R338K
6% of wild-type activity
Escherichia coli
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.1.3.1
additional information
natural glyoxylate cycle inhibitors such 5-hydroxyindole-type alkaloids are potent inhibitors
Candida albicans
4.1.3.1
additional information
halisulfates from the tropical sponge Hippospongia sp. are able to inhibit ICL activity, appressorium formation and C2 utilization
Magnaporthe grisea
4.1.3.1
additional information
extracts of Illicium verum and Zingiber officinale inhibit ICL
Mycobacterium tuberculosis
Localization
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
4.1.3.1
peroxisome
-
Colletotrichum lagenaria
5777
-
Metals/Ions
EC Number
Metals/Ions
Commentary
Organism
Structure
2.3.3.9
Mg2+
-
Escherichia coli
Molecular Weight [Da]
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
2.3.3.9
65000
-
x * 65000
Escherichia coli
2.3.3.9
80000
-
1 * 80000
Escherichia coli
4.1.3.1
50000
-
-
Mycobacterium tuberculosis
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.3.3.9
Bradyrhizobium japonicum
-
-
-
2.3.3.9
Candida albicans
-
-
-
2.3.3.9
Escherichia coli
-
-
-
2.3.3.9
Mycobacterium tuberculosis
-
-
-
2.3.3.9
Paracoccidioides brasiliensis
-
-
-
2.3.3.9
Parastagonospora nodorum
-
-
-
2.3.3.9
Rhizobium leguminosarum
-
-
-
2.3.3.9
Rhodococcus fascians
-
-
-
2.3.3.9
Sinorhizobium meliloti
-
-
-
2.3.3.9
Xanthomonas campestris
-
-
-
2.3.3.9
Yersinia enterocolitica
-
-
-
2.3.3.9
Yersinia pestis
-
-
-
2.3.3.9
Yersinia pseudotuberculosis
-
-
-
4.1.3.1
Aspergillus fumigatus
-
-
-
4.1.3.1
Aspergillus nidulans
-
-
-
4.1.3.1
Brucella suis
-
-
-
4.1.3.1
Candida albicans
-
-
-
4.1.3.1
Colletotrichum lagenaria
-
-
-
4.1.3.1
Cryptococcus neoformans
-
-
-
4.1.3.1
Escherichia coli
-
-
-
4.1.3.1
Leptosphaeria maculans
-
-
-
4.1.3.1
Magnaporthe grisea
-
-
-
4.1.3.1
Mycobacterium avium
-
-
-
4.1.3.1
Mycobacterium tuberculosis
-
-
-
4.1.3.1
Paracoccidioides brasiliensis
-
-
-
4.1.3.1
Pseudomonas aeruginosa
-
-
-
4.1.3.1
Rhizobium tropici
-
-
-
4.1.3.1
Rhodococcus hoagii
-
-
-
4.1.3.1
Salmonella enterica subsp. enterica serovar Typhimurium
-
-
-
4.1.3.1
Sinorhizobium meliloti
-
-
-
4.1.3.1
Talaromyces marneffei
-
-
-
4.1.3.1
Yersinia enterocolitica
-
-
-
4.1.3.1
Yersinia pestis
-
-
-
4.1.3.1
Yersinia pseudotuberculosis
-
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
4.1.3.1
appressorium
-
Colletotrichum lagenaria
-
4.1.3.1
appressorium
-
Magnaporthe grisea
-
4.1.3.1
conidium
-
Aspergillus fumigatus
-
4.1.3.1
conidium
-
Colletotrichum lagenaria
-
4.1.3.1
conidium
-
Magnaporthe grisea
-
4.1.3.1
hypha
-
Aspergillus fumigatus
-
4.1.3.1
hypha
-
Colletotrichum lagenaria
-
4.1.3.1
hypha
-
Magnaporthe grisea
-
4.1.3.1
mycelium
-
Magnaporthe grisea
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.1.3.1
isocitrate
-
705567
Pseudomonas aeruginosa
succinate + glyoxylate
-
-
-
?
4.1.3.1
additional information
Lys-193, Cys-195, His-197 and His-356 are catalytic, active-site residues, while His-184 is involved in the assembly of the tetrameric enzyme
705567
Escherichia coli
?
-
-
-
-
Subunits
EC Number
Subunits
Commentary
Organism
2.3.3.9
monomer
1 * 80000
Escherichia coli
2.3.3.9
multimer
x * 65000
Escherichia coli
4.1.3.1
tetramer
-
Escherichia coli
Activating Compound (protein specific)
EC Number
Activating Compound
Commentary
Organism
Structure
4.1.3.1
additional information
high enzymic activity of ICL in strains isolated from diabetic patients suffering from vulvovaginal candidiasis. Specific activation of ICL1 when the pathogen is exposed to neutrophils or macrophages
Candida albicans
4.1.3.1
additional information
ICL activity increases in pellicles in synthetic media as a consequence of fatty acid degradation as well as under microaerophilic growth conditions
Mycobacterium tuberculosis
Application (protein specific)
EC Number
Application
Commentary
Organism
4.1.3.1
additional information
constitutive enzymic activity can be used to identify Yersinia pestis in humans, animals, water, soil and food
Yersinia pestis
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
2.3.3.9
D631N
no activity
Escherichia coli
2.3.3.9
R338K
6% of wild-type activity
Escherichia coli
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.1.3.1
additional information
natural glyoxylate cycle inhibitors such 5-hydroxyindole-type alkaloids are potent inhibitors
Candida albicans
4.1.3.1
additional information
halisulfates from the tropical sponge Hippospongia sp. are able to inhibit ICL activity, appressorium formation and C2 utilization
Magnaporthe grisea
4.1.3.1
additional information
extracts of Illicium verum and Zingiber officinale inhibit ICL
Mycobacterium tuberculosis
Localization (protein specific)
EC Number
Localization
Commentary
Organism
GeneOntology No.
Textmining
4.1.3.1
peroxisome
-
Colletotrichum lagenaria
5777
-
Metals/Ions (protein specific)
EC Number
Metals/Ions
Commentary
Organism
Structure
2.3.3.9
Mg2+
-
Escherichia coli
Molecular Weight [Da] (protein specific)
EC Number
Molecular Weight [Da]
Molecular Weight Maximum [Da]
Commentary
Organism
2.3.3.9
65000
-
x * 65000
Escherichia coli
2.3.3.9
80000
-
1 * 80000
Escherichia coli
4.1.3.1
50000
-
-
Mycobacterium tuberculosis
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
4.1.3.1
appressorium
-
Colletotrichum lagenaria
-
4.1.3.1
appressorium
-
Magnaporthe grisea
-
4.1.3.1
conidium
-
Aspergillus fumigatus
-
4.1.3.1
conidium
-
Colletotrichum lagenaria
-
4.1.3.1
conidium
-
Magnaporthe grisea
-
4.1.3.1
hypha
-
Aspergillus fumigatus
-
4.1.3.1
hypha
-
Colletotrichum lagenaria
-
4.1.3.1
hypha
-
Magnaporthe grisea
-
4.1.3.1
mycelium
-
Magnaporthe grisea
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.1.3.1
isocitrate
-
705567
Pseudomonas aeruginosa
succinate + glyoxylate
-
-
-
?
4.1.3.1
additional information
Lys-193, Cys-195, His-197 and His-356 are catalytic, active-site residues, while His-184 is involved in the assembly of the tetrameric enzyme
705567
Escherichia coli
?
-
-
-
-
Subunits (protein specific)
EC Number
Subunits
Commentary
Organism
2.3.3.9
monomer
1 * 80000
Escherichia coli
2.3.3.9
multimer
x * 65000
Escherichia coli
4.1.3.1
tetramer
-
Escherichia coli
Expression
EC Number
Organism
Commentary
Expression
2.3.3.9
Parastagonospora nodorum
decrease in transcription after germination, increase of activity after germination
down
2.3.3.9
Candida albicans
in the presence of macrophages
up
2.3.3.9
Paracoccidioides brasiliensis
in the presence of macrophages
up
2.3.3.9
Xanthomonas campestris
during infection of tomato plants
up
2.3.3.9
Yersinia enterocolitica
during growth on acetate
up
2.3.3.9
Yersinia pseudotuberculosis
during growth on acetate
up
4.1.3.1
Candida albicans
in bloodstream infection, ICL is downregulated in the initial stages of infection (10 min)
down
4.1.3.1
Candida albicans
is induced in Candida albicans exposed to human neutrophils. In bloodstream infection, ICL is upregulated beginning about 20 min after infection and reaches a 20fold increase after 60 min. ICL expression is detected during growth on Casamino acids, glutamate or peptone, and under starvation conditions
up
4.1.3.1
Cryptococcus neoformans
ICL in a rabbit meningitis model is upregulated after 7 days in the subarachnoid space
up
4.1.3.1
Magnaporthe grisea
during infection, significant ICL gene expression in conidia, appressoria, mycelia and hyphae
up
4.1.3.1
Mycobacterium tuberculosis
increased aceA (icl) mRNA expression in response to human macrophages. ICL mRNA levels markedly increase in lungs of mice and in human lung granulomas, as well as in the lymphocyte region of necrotic granulomas
up
4.1.3.1
Paracoccidioides brasiliensis
transcript level of the ICL gene increases following phagocytosis by murine macrophages. After macrophage internalization of conidia the ICL-encoding gene (acuD) is highly expressed
up
4.1.3.1
Talaromyces marneffei
expressed in macrophages
up
4.1.3.1
Yersinia enterocolitica
induced during growth on acetate but not on xylose
up
4.1.3.1
Yersinia pseudotuberculosis
induced during growth on acetate but not on xylose
up
General Information
EC Number
General Information
Commentary
Organism
4.1.3.1
malfunction
a mutant deleted of the ICL gene (acuD) is fully virulent in a murine model
Aspergillus fumigatus
4.1.3.1
malfunction
an ICL-deficient mutant is unable to utilize acetate, ethanol, citrate, glycerol, oleate, lactate, pyruvate, peptone, glutamate or alanine for growth, unlike the parental strain. ICL-deficient mutant is unable to utilize nonfermentable carbon sources and has reduced virulence in mice
Candida albicans
4.1.3.1
malfunction
ICL1 mutant fails to grow on acetate or fatty acids, but is able to germinate and develop appressoria and is capable of degrading lipid bodies as well as the wild-type strain. Conidia from the ICL1-deficient mutant inoculated onto cucumber leaves and cotyledons form a reduced number of lesions on leaves, and especially on cotyledons, but nevertheless remain pathogenic. In invasive experiments such as the inoculation of conidia into wound sites, no defect is observed in the ICL1 mutant, while in penetration assays on cucumber cotyledons the mutant is unable to develop penetrating hyphae
Colletotrichum lagenaria
4.1.3.1
malfunction
an ICL1 mutant shows the same number of subarachnoidal yeast cells as the wild-type after 10 days in immunosuppressed rabbits. In an inhalation model of murine cryptococcosis, no differences in survival between an ICL1 mutant and the wild-type
Cryptococcus neoformans
4.1.3.1
malfunction
deletion of the ICL1 gene causes a reduction in appressorium formation, conidiogenesis and cuticle penetration, and an overall decrease in damage to leaves of rice and barley
Magnaporthe grisea
4.1.3.1
malfunction
single ICL mutations have no dramatic effect on the growth. ICL mutant has a reduced ability to sustain the infection. An ICL/AceA double mutant is unable to grow on carbon source. The double mutant inoculated into mice is eliminated from lungs and spleen and is unable to induce splenomegaly or alterations in lungs
Mycobacterium tuberculosis
4.1.3.1
malfunction
ICL (aceA) mutant displays reduced virulence on alfalfa seedlings and a reduction in histopathology in rat lungs
Pseudomonas aeruginosa
4.1.3.1
malfunction
population of an ICL-deficient strain increases in macrophages after 12 h but then decline significantly
Rhodococcus hoagii
4.1.3.1
malfunction
mutations in the sole ICL gene (aceA) prevent growth on acetate but do not affect pathogenesis in a mouse model
Yersinia pestis
4.1.3.1
physiological function
the glyoxylate cycle mediated by ICL is unnecessary for virulence
Brucella suis
4.1.3.1
physiological function
ICL1 contributes to virulence but is not essential for systemic infection. Role for the beta-oxidation pathway in virulence
Candida albicans
4.1.3.1
physiological function
lack of correlation between ICL gene expression and biological function
Cryptococcus neoformans
4.1.3.1
physiological function
important role for ICL in fungal virulence on plants. The ICL1 gene is expressed during its infection of Brassica napus cotyledons and inactivation of this locus causes low germination rates of pycnidiospores, reducing the pathogenicity of the fungus on cotyledons as well as limiting its hyphal growth on canola
Leptosphaeria maculans
4.1.3.1
physiological function
ICL is essential for full virulence in the organism
Magnaporthe grisea
4.1.3.1
physiological function
two functional ICLs
Mycobacterium avium
4.1.3.1
physiological function
two functional ICLs. ICL has a pivotal role in bacterial persistence in the host. ICL activity is essential for survival in the host. ICL and to a lesser extent AceA are required for the growth on propionate and on odd-chain fatty acids as a carbon source. The organism possesses dual ICL/MICL activity and can support growth on acetate and propionate
Mycobacterium tuberculosis
4.1.3.1
physiological function
ICL is essential for long-term survival and proliferation in macrophages
Rhodococcus hoagii
4.1.3.1
physiological function
ICL is required for persistence during chronic infection, but not for acute lethal infection in mice
Salmonella enterica subsp. enterica serovar Typhimurium
4.1.3.1
physiological function
the organism constitutively produces ICL
Yersinia pestis
General Information (protein specific)
EC Number
General Information
Commentary
Organism
4.1.3.1
malfunction
a mutant deleted of the ICL gene (acuD) is fully virulent in a murine model
Aspergillus fumigatus
4.1.3.1
malfunction
an ICL-deficient mutant is unable to utilize acetate, ethanol, citrate, glycerol, oleate, lactate, pyruvate, peptone, glutamate or alanine for growth, unlike the parental strain. ICL-deficient mutant is unable to utilize nonfermentable carbon sources and has reduced virulence in mice
Candida albicans
4.1.3.1
malfunction
ICL1 mutant fails to grow on acetate or fatty acids, but is able to germinate and develop appressoria and is capable of degrading lipid bodies as well as the wild-type strain. Conidia from the ICL1-deficient mutant inoculated onto cucumber leaves and cotyledons form a reduced number of lesions on leaves, and especially on cotyledons, but nevertheless remain pathogenic. In invasive experiments such as the inoculation of conidia into wound sites, no defect is observed in the ICL1 mutant, while in penetration assays on cucumber cotyledons the mutant is unable to develop penetrating hyphae
Colletotrichum lagenaria
4.1.3.1
malfunction
an ICL1 mutant shows the same number of subarachnoidal yeast cells as the wild-type after 10 days in immunosuppressed rabbits. In an inhalation model of murine cryptococcosis, no differences in survival between an ICL1 mutant and the wild-type
Cryptococcus neoformans
4.1.3.1
malfunction
deletion of the ICL1 gene causes a reduction in appressorium formation, conidiogenesis and cuticle penetration, and an overall decrease in damage to leaves of rice and barley
Magnaporthe grisea
4.1.3.1
malfunction
single ICL mutations have no dramatic effect on the growth. ICL mutant has a reduced ability to sustain the infection. An ICL/AceA double mutant is unable to grow on carbon source. The double mutant inoculated into mice is eliminated from lungs and spleen and is unable to induce splenomegaly or alterations in lungs
Mycobacterium tuberculosis
4.1.3.1
malfunction
ICL (aceA) mutant displays reduced virulence on alfalfa seedlings and a reduction in histopathology in rat lungs
Pseudomonas aeruginosa
4.1.3.1
malfunction
population of an ICL-deficient strain increases in macrophages after 12 h but then decline significantly
Rhodococcus hoagii
4.1.3.1
malfunction
mutations in the sole ICL gene (aceA) prevent growth on acetate but do not affect pathogenesis in a mouse model
Yersinia pestis
4.1.3.1
physiological function
the glyoxylate cycle mediated by ICL is unnecessary for virulence
Brucella suis
4.1.3.1
physiological function
ICL1 contributes to virulence but is not essential for systemic infection. Role for the beta-oxidation pathway in virulence
Candida albicans
4.1.3.1
physiological function
lack of correlation between ICL gene expression and biological function
Cryptococcus neoformans
4.1.3.1
physiological function
important role for ICL in fungal virulence on plants. The ICL1 gene is expressed during its infection of Brassica napus cotyledons and inactivation of this locus causes low germination rates of pycnidiospores, reducing the pathogenicity of the fungus on cotyledons as well as limiting its hyphal growth on canola
Leptosphaeria maculans
4.1.3.1
physiological function
ICL is essential for full virulence in the organism
Magnaporthe grisea
4.1.3.1
physiological function
two functional ICLs
Mycobacterium avium
4.1.3.1
physiological function
two functional ICLs. ICL has a pivotal role in bacterial persistence in the host. ICL activity is essential for survival in the host. ICL and to a lesser extent AceA are required for the growth on propionate and on odd-chain fatty acids as a carbon source. The organism possesses dual ICL/MICL activity and can support growth on acetate and propionate
Mycobacterium tuberculosis
4.1.3.1
physiological function
ICL is essential for long-term survival and proliferation in macrophages
Rhodococcus hoagii
4.1.3.1
physiological function
ICL is required for persistence during chronic infection, but not for acute lethal infection in mice
Salmonella enterica subsp. enterica serovar Typhimurium
4.1.3.1
physiological function
the organism constitutively produces ICL
Yersinia pestis
Expression (protein specific)
EC Number
Organism
Commentary
Expression
2.3.3.9
Parastagonospora nodorum
decrease in transcription after germination, increase of activity after germination
down
2.3.3.9
Candida albicans
in the presence of macrophages
up
2.3.3.9
Paracoccidioides brasiliensis
in the presence of macrophages
up
2.3.3.9
Xanthomonas campestris
during infection of tomato plants
up
2.3.3.9
Yersinia enterocolitica
during growth on acetate
up
2.3.3.9
Yersinia pseudotuberculosis
during growth on acetate
up
4.1.3.1
Candida albicans
in bloodstream infection, ICL is downregulated in the initial stages of infection (10 min)
down
4.1.3.1
Candida albicans
is induced in Candida albicans exposed to human neutrophils. In bloodstream infection, ICL is upregulated beginning about 20 min after infection and reaches a 20fold increase after 60 min. ICL expression is detected during growth on Casamino acids, glutamate or peptone, and under starvation conditions
up
4.1.3.1
Cryptococcus neoformans
ICL in a rabbit meningitis model is upregulated after 7 days in the subarachnoid space
up
4.1.3.1
Magnaporthe grisea
during infection, significant ICL gene expression in conidia, appressoria, mycelia and hyphae
up
4.1.3.1
Mycobacterium tuberculosis
increased aceA (icl) mRNA expression in response to human macrophages. ICL mRNA levels markedly increase in lungs of mice and in human lung granulomas, as well as in the lymphocyte region of necrotic granulomas
up
4.1.3.1
Paracoccidioides brasiliensis
transcript level of the ICL gene increases following phagocytosis by murine macrophages. After macrophage internalization of conidia the ICL-encoding gene (acuD) is highly expressed
up
4.1.3.1
Talaromyces marneffei
expressed in macrophages
up
4.1.3.1
Yersinia enterocolitica
induced during growth on acetate but not on xylose
up
4.1.3.1
Yersinia pseudotuberculosis
induced during growth on acetate but not on xylose
up