Possible role for cysteine biosynthesis in conversion from mycelial to yeast form of Histoplasma capsulatum

Abstract

Histoplasma capsulatum is a pathogenic dimorphic fungus which causes histoplasmosis in animals and man. The free-living saprobic form found in soil is mycelial, but, on infection, or in the laboratory, when the temperature is raised from 23 to 37 °C, it converts reversibly to a unicellular, parasitic yeast-like form. Little is known about the biochemistry of this process. There have been reports of quantitative and qualitative differences in the chemical composition of the two forms^1,2, and of changes in RNA metabolism during the conversion³. Also, whereas extracts from the yeast phase cells contain multiple species of RNA polymerase, those from mycelia have only traces of activity, but contain an inhibitor of RNA polymerase⁴. The yeast and mycelial cells differ in sensitivity to amphotericin B (a polyene) and actinomycin D⁵, but there is no significant enzymatic difference between the two phases with respect to the glycolytic pathway and the tricarboxylic acid cycle⁶. The initiation of conversion requires a temperature change and also low oxidation–reduction potential (O/R) of the growth medium⁷, but the maintenance of the yeast phase requires sulphur-containing organic compounds, especially cysteine^8,9. The possibility of a nutritional requirement for –SH groups has been suggested¹⁰ but not explored. We now report that the yeast cells lack the enzyme sulphite reductase so that they cannot reduce inorganic sulphite to sulphide, and thus cannot synthesise cysteine. In contrast, mycelial cells, with active reductase, can grow without cysteine supplement.