In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride and valproic acid sodium salt with antifungal agents against filamentous fungal species causing central nervous system infection.

The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

Variation of isoenzyme and RAPD patterns in Candida albicans morphological mutants with altered colony ultrastructure.

Molecular typing methods were applied to characterize four stable morphological mutants [1] isolated from a UV-induced unstable mutant colony of Candida albicans. The wild-type strain (ATCC 64385), the intermediate unstable mutant and its four morphologically altered derivatives revealed the same electrophoretic karyotypes. Of the five isoenzymes tested (catalase, malate dehydrogenase, glutamate dehydrogenase, acid phosphatase and 3-glucosidase), glutamate dehydrogenase displayed a different enzyme pattern (with an extra band of lower mobility) in the morphological mutants. In contrast, the random amplification DNA polymorphism patterns of the mutant strains differed in all cases from that of the parental strain. Different primers revealed various degrees of DNA polymorphism; one of them (OPC-8) proved to be useful for differentiation between all examined strains. Differences in genetic alterations between spontaneous and induced mutants, and the applicability of different molecular markers to analyse the consequences of induced mutagenesis in C. albicans are discussed.

Variability of isozyme and rapd markers among isolates of Mucor genevensis.

Mucor genevensis is a dimorphic and homothallic fungal species (Zygomycetes). Ten M. genevensis strains, each strain of the recently described new homothallic species (M. meguroense and M. hachijyoensis) and strains of M. hiemalis and M. piriformis (as outgroups for numerical analysis) were investigated. Five different enzyme systems (CAT, GDH, G6D, MDH and SOD) and five 10-bp random primers were used in isoenzyme and random amplified polymorphic DNA analyses, respectively. The data from these studies were subjected to numerical analyses. Substantial intraspecific variability was detected in M. genevensis with both of the methods applied. Though both the M. meguroense strain and the M. hachijyoensis strain revealed characteristic differences, they grouped closer to the homothallic M. genevensis than to the heterothallic M. piriformis and M. hiemalis strains.