Isocitrate lyase and malate synthase activities of Coccidioides immitis

Abstract

The saprophytic phase of the fungal pathogen Coccidioides immitis contains both of the enzymes unique to the glyoxylate cycle (isocitrate lyase, EC 4.1.3.1, and malate synthase, EC 4.1.3.2) when grown in a variety of media regardless of whether or not glucose is present in those media. Significantly higher levels of each enzyme are found in cells grown in defined media. Enzyme activity varied as a function of growth, being higher during the germination phase than the exponential phase of growth. C. immitis arthroconidia do not germinate in medium containing glucose as the sole carbon source, but will germinate in this same medium with acetate as the carbon source. Glucose alone does not support vegetative growth and acetate is utilized preferentially over glucose when both are present in defined minimal medium. An inhibitor of isocitrate lyase, itaconic acid, inhibits germination and vegetative growth of C. immitis in all growth supporting media tested. Itaconic acid acts synergistically with amphotericin B to inhibit arthroconidia germination and growth.