ABSTRACT
The susceptibility of Aspergillus fumigatus to a series of alpha, beta-unsaturated styryl ketones known to be thiol-alkylators was examined, and the results were compared with those obtained for Candida albicans. Among 13 compounds used in our study, one (designated NC1110) inhibited the growth of A. fumigatus completely at low concentrations (minimum inhibitory concentration = 32 microM). Structure-activity analysis of these compounds indicated that the electron attracting property as well as the overall hydrophobicity of the compounds are important parameters for their antifungal activity. These preliminary results suggest that further modification of these molecules to enhance their hydrophobicity and the electron attracting property may result in more active compounds with improved antifungal activity.
Subject(s)
Antifungal Agents/chemistry , Aspergillus fumigatus/drug effects , Candida albicans/drug effects , Ketones/chemistry , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity RelationshipABSTRACT
The glycolytic enzyme phosphoglycerate kinase (PGK) is highly conserved throughout the evolutionary ladder. Using a previously cloned Saccharomyces cerevisiae PGK gene as hybridization probe, chromosomal localization and strain-specific variation of PGK gene in C. albicans have been examined. Separation of chromosome-size DNA fragments by pulse field gel electrophoresis followed by DNA- DNA hybridization analysis revealed that the PGK is encoded by a single copy gene located on the large chromosome of the commonly used laboratory strain ATCC 32354, as well as of several clinical isolates of C. albicans. Restriction fragment length analysis indicated that the PGK gene locus is highly polymorphic, and this strain-specific variation could be exploited to study intra-specific relatedness of clinical isolates.