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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.
    View publication on PubMedView publication on EuropePMC

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
-
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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