Literature summary extracted from
van Schaik, E.J.; Tom, M.; Woods, D.E.
Burkholderia pseudomallei isocitrate lyase is a persistence factor in pulmonary melioidosis: implications for the development of isocitrate lyase inhibitors as novel antimicrobials (2009), Infect. Immun., 77, 4275-4283.
Activating Compound
EC Number |
Activating Compound |
Comment |
Organism |
Structure |
---|
4.1.3.1 |
acetate |
activity of the ICL promoter is significantly upregulated during growth on acetate |
Burkholderia pseudomallei |
|
Application
EC Number |
Application |
Comment |
Organism |
---|
4.1.3.1 |
drug development |
isocitrate lyase inhibitors can be developed for chronic infections but only for use in combination with effective antibiotics |
Burkholderia pseudomallei |
Cloned(Commentary)
EC Number |
Cloned (Comment) |
Organism |
---|
4.1.3.1 |
pGSV3-lux ICL mutant |
Burkholderia pseudomallei |
Inhibitors
EC Number |
Inhibitors |
Comment |
Organism |
Structure |
---|
4.1.3.1 |
Itaconic acid |
potent competitive inhibitor of ICL, 1 mg/ml reduces the activity to 42% of the uninhibited control. Inhibition of ICL enzymatic activity during chronic infection of rats forces the infection into an acute phase |
Burkholderia pseudomallei |
|
Organism
EC Number |
Organism |
UniProt |
Comment |
Textmining |
---|
4.1.3.1 |
Burkholderia pseudomallei |
- |
strains 1026b and DD503 |
- |
Source Tissue
EC Number |
Source Tissue |
Comment |
Organism |
Textmining |
---|
Substrates and Products (Substrate)
EC Number |
Substrates |
Comment Substrates |
Organism |
Products |
Comment (Products) |
Rev. |
Reac. |
---|
4.1.3.1 |
isocitrate |
- |
Burkholderia pseudomallei |
succinate + glyoxylate |
- |
? |
|
Synonyms
EC Number |
Synonyms |
Comment |
Organism |
---|
4.1.3.1 |
ICL |
- |
Burkholderia pseudomallei |
4.1.3.1 |
isocitrate lyase |
- |
Burkholderia pseudomallei |
General Information
EC Number |
General Information |
Comment |
Organism |
---|
4.1.3.1 |
malfunction |
inhibiting the activity of this enzyme during experimental chronic lung infection of rats forces the infection into an acute state, which can then be treated with antibiotics. If antibiotics are not provided in combination with isocitrate lyase inhibitors, the resulting infection overwhelms the host, resulting in death. ICL mutant is hypervirulent, it does not establish a chronic infection but establishes an acute infection. ICL mutants are significantly more cytotoxic than other strains. Complementation of the mutant strain restores the wild-type phenotype |
Burkholderia pseudomallei |
4.1.3.1 |
physiological function |
isocitrate lyase is a persistence factor. ICL is not required for survival within unactivated murine macrophage cells |
Burkholderia pseudomallei |