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W H Beggs

Publications and source records attributed to W H Beggs.

At least 19 recordsLinked to original sources
PubMed1995

Growth phase in relation to the lethal action of tamoxifen on Candida albicans.

Tamoxifen, a drug used to treat breast cancer, might have antifungal potential. The fungicidal activity of tamoxifen against Candida albicans surpassed that of the most active of the imidazole-type drugs. At 15-20 microM, tamoxifen rapidly killed yeast cells in stationary phase as well as in logarithmic phase, whereas imidazoles at this level generally do not exert significant lethal activity against stationary phase organisms.

Candida albicans↗
PubMed1994

Physicochemical cell damage in relation to lethal amphotericin B action.

A direct relationship between the concentration-dependent rate of amphotericin B-induced K+ release from Candida albicans and the concentration-dependent rate of killing by the drug was established. This relationship together with the observed rapidity of both release and killing action supports the conclusion that the lethal action of amphotericin B is primarily physicochemical in nature.

Amphotericin B↗
PubMed1993

Anti-Candida activity of the anti-cancer drug tamoxifen.

Earlier workers found that tamoxifen, a drug widely used to treat breast cancer, can exert a marked antifungal action against the non-pathogenic yeast Saccharomyces cerevisiae. In this report, the earlier observation has been extended to Candida albicans, the most important of the opportunistic fungal pathogens. Experiments in which antifungal effect against logarithmic phase cells was monitored by viable count as a function of drug exposure time clearly showed that tamoxifen is highly fungicidal at 2.0 x 10(-5) M, moderately and transiently fungicidal at 1.0 x 10(-5) M, but only very weakly fungistatic at 5.0 x 10(-6) M.

Antifungal Agents↗
PubMed1992

Influence of alkaline pH on the direct lethal action of miconazole against Candida albicans.

The imidazole group of miconazole is subject to protonation (pKa approximately 6.5). Earlier we suggested that the direct lethal action (DLA) of miconazole against Candida albicans requires nonprotonated drug molecules. DLA declined in intensity as pH was decreased from 6.0. At pH > 6.5 most molecules of miconazole exist in the nonprotonated state, but drug also becomes less soluble. Viability studies were designed to assess DLA in relation to alkaline pH. DLA was clearly inhibited with increasing as well as decreasing pH (i.e., pH < 6.0 and > 7.0), suggesting that nonprotonated neutral drug molecules must be in solution or in extremely small aggregates to elicit DLA, and that the nonprotonated species itself is more soluble at pH 6.0-7.0 than under more alkaline conditions.

Candida albicans↗
PubMed1992

Direct membrane damage and miconazole lethality.

Physicochemical membrane damage is presumably the cause of growth phase-dependent lethal miconazole action. In support of this, we showed that as stationary phase inoculum cells of Candida albicans progress into early logarithmic phase, susceptibilities to lethal action and to miconazole-induced release of K+ increase together.

Candida albicans↗
PubMed1990

Potential of bifonazole for direct lethal action.

Time-kill type experiments were designed to assess the potential of bifonazole, a topical antifungal imidazole-containing drug, for its capacity to exert growth phase-dependent direct physicochemical lethal action against opportunistic yeast pathogens. Test organisms included two strains of Candida albicans and one of Candida parapsilosis. In contrast to the reference imidazole miconazole, which rapidly killed yeast cells in late lag to early logarithmic phase at concentrations between 10(-5) and 10(-4) M, bifonazole was inhibitory but not lethal. Bifonazole appears to lack a significant capacity for growth phase-dependent direct lethal action against Candida species.

Antifungal Agents↗
PubMed1990

Further studies on factors controlling phenotypic susceptibility of Candida albicans to miconazole kill.

A growth-limiting medium was used for further studies on growth phase-dependent shifts in susceptibility of Candida albicans to direct lethal miconazole action. Restricted nutrition did not affect development of susceptibility. Reestablishment of resistance toward stationary phase was not a physiological response to nutrient exhaustion. Resistance developed even at low population density if cells were in physiological transition to stationary phase with glucose available.

Candida albicans↗
PubMed1989

Development of phenotypic resistance to direct lethal miconazole action by Candida albicans entering stationary phase.

In the late logarithmic or very early stationary phase of the growth cycle, yeast cells of Candida albicans undergo a shift from susceptibility to resistance to the direct lethal action of miconazole. Regulation of this phenotypic shift was examined. Experiments based on viable count determinations and the construction of time-kill curves showed that reestablishment of resistance is independent of both pH and the attainment of some critical viable cell density. However, it was found that development of resistance requires the continued availability of an appropriate energy source toward the end of exponential growth.

Candida albicans↗
PubMed1989

Fungistatic activity of miconazole against Candida albicans in relation to pH and concentration of nonprotonated drug.

At less than 10(-5) M, miconazole (MCZ) exerts a fungistatic effect on Candida albicans, presumably by interfering with ergosterol biosynthesis. The imidazole moiety of MCZ is subject to protonation (pKa approximately 6.5). Based on pKa and greater water solubility of protonated (MCZH+) versus nonprotonated (MCZo) drug, fungistatic action ought to be markedly affected by environmental pH, but apparently it is not. In this report growth phase, pH, and concentrations of MCZ and MCZo have been studied in relation to fungistasis. Yeasts were grown in a synthetic liquid medium and MCZ effects were monitored by viability determinations. Results showed that fungistatic activity is little affected by growth phase and is largely independent of drug concentration and pH. Antagonism of fungistasis by low pH was demonstrated only at less than 10(-7) M MCZ. Data supported earlier proposals that MCZo is required for biological activity and suggested that target sites are saturated at very low levels of drug.

Candida albicans↗
PubMed1988

Requirement for nonprotonated drug molecules in the direct lethal action of miconazole against Candida albicans.

At greater than or equal to 10(-5) M, miconazole (MCZ) can exert a direct physicochemical cell-damaging lethal action against logarithmic phase yeasts of Candida albicans. The imidazole moiety of MCZ has a pKa approximately 6.5. Thus, in media of pH greater than 6.5 most drug molecules are nonprotonated (MCZ degrees). Conversely, at pH less than 6.5 the majority are protonated and carry a positive charge (MCZH+). Our earlier work suggesting that MCZ degrees is required for direct lethal action was tested further. In support of such a requirement, we established a minimal lethal concentration of MCZ degrees (i.e. 5 x 10(-6) M) that was relatively independent of pH, MCZ concentration, and MCZ degrees:MCZH+ ratio.

Antifungal Agents↗
PubMed1988

Antagonism of the direct fungicidal action of miconazole by miconazole fungistasis.

A weakly fungistatic concentration of miconazole in lag phase yeast cultures of Candida albicans antagonized development of phenotypic susceptibility to the direct fungicidal action of high-level (i.e. greater than 10(-5) M) miconazole. After development in the absence of drug, maintenance of susceptibility upon continued incubation was also antagonized by low levels of miconazole. This auto-antagonistic effect has important clinical implications.

Candida albicans↗