Carica papaya latex sap inhibits the growth of Candida albicans when added to a culture during the exponential growth phase. Approximately 60% was achieved. This fungistatic effect is the result of cell wall degradation due to a lack of polysaccharidic constituents in the outermost layers of the fungal cell wall and release of cell debris into the culture medium. When C. albicans was cultured on medium supplemented with D(+)-glucosamine, an inhibitor of N-acetyl-beta-D-glucosaminidase, growth was inhibited (34%) in a similar manner. Addition of D(+)-glucosamine during the exponential growth phase also had a fungistatic effect (26%). The modes of action of C. papaya latex and of D(+)-glucosamine in cell wall breakdown are discussed.
Summary. Carica papaya latex inhibits the growth of Candida albicans. Latex proteins appear to be responsible for this antifungal effect. The minimum protein concentration for producing a complete inhibition was estimated to be about 138 μg ml‐1. Exploration of different glycosidic activities shows that only α‐D‐mannosidase and N‐acetyl‐β‐D‐glucosaminidase were present in latex in important levels and they were partially purified. The two enzymes show a limited inhibitory effect on yeast growth, α‐D‐mannosidase being more efficient than N‐acetyl‐β‐D‐glucosaminidase. A mixture of the two enzymes showed a synergistic action on the inhibition of the yeast growth. Scanning and transmission electron microscopy observations showed a lack of polysac‐charidic content on outermost layers of yeast cell walls when α‐D‐mannosidase was added to the culture medium. When C. albicans was cultured in medium supplemented with N‐acetyl‐β‐D‐glucosaminidase a lack of polysaccharides was noted not only in the outermost layers of fungal cell wall but also in the inner layers. The potential utilization of latex glycosidases in combination with antifungals such as polyenes and azoles involving the formation of protoplasts is discussed. Zusammenfassung. Carica papaya‐Milchsaft hemmt das Wachstum von Candida albicans. Für diese Wirkung sind offenbar Milchsaft‐Proteine verantwortlich. Die minimale, komplett hemmende Protein‐Konzentration liegt bei 138 μg ml‐1. Die Untersuchung der einzelnen Glykosidase‐Aktivitäten ergab, daß nur α‐D‐Mannosidase und N‐Acetyl‐β‐D‐Glucosaminidase in nennenswerten Konzentrationen im Milchsaft vorkommen und daß diese Enzyme teilweise rein vorliegen. Beide Enzyme bewirken einen begrenzten Hemmeffekt auf das Hefewachstum. α‐D‐Mannosidase ist wirksamer als N‐Acetyl‐β‐D‐Glucosaminidase. Die Mischung beider zeigt einen synergistischen Effekt auf die Hefewachstumshemmung. Raster‐ und transmissionselek‐tronenmikroskopische Beobachtungen zeigten bei Zusatz von α‐D‐Mannosidase zum Kulturmedium eine Verarmung des Polysaccharidgehaltes der äußersten Hefezellwandschichten. Wurde C. albicans in N‐Acetyl‐β‐D‐Glucosaminidase‐haltigem Nährmedium kultiviert, verarmten die Hefezellwände nicht nur in den äußeren, sondern auch in den inneren Schichten an Polysacchari‐den. Die potentielle Nutzung von Milchsaft‐Glykosidasen in Kombination mit Antimyzetika wie Polyenen und Azolen zur Protoplastenbil‐dung bei Hefen wird diskutiert.
A mixture of Carica papaya latex (0.41 mg protein ml-1) and fluconazole (2 micrograms ml-1) showed a synergistic action on the inhibition of Candida albicans growth. Thus, with this mixture an equivalent inhibition rate was observed to that obtained when C. albicans was cultured in a medium supplemented with a two-fold concentration (4 micrograms ml-1) of fluconazole alone. This synergistic effect resulted in partial cell wall degradation as indicated by transmission electron microscopy observations. An increase of fluconazole concentration from 2 micrograms ml-1 to 4 micrograms ml-1 involved a small decrease of MIC 80% from latex (150 to 130 micrograms protein ml-1). Measure of MIC 80% from fluconazole mixed with latex in a subinhibitory concentration (85 micrograms protein ml-1) allows the determination of an effective fluconazole concentration (4 micrograms ml-1) inferior to mean plasmatic dose observed in human therapy. The potential therapeutic use of latex in combination with a synthetic antifungal is discussed.
alpha-Hederin, a saponin isolated from Hedera helix (L.) (Araliaceae), was tested on Candida albicans ultrastructure. The concentrations used were 6.25, 12.5, and 25 micrograms ml-1 for an exposure time of 24 h. Transmission electron microscopy observations indicated that compared with untreated control yeasts, alpha-hederin induced modifications of cellular contents and alterations of cell envelope with degradation and death of the yeasts. The impact of alpha-hederin on the biomembranes and in particular on the plasmalemma is discussed. The antifungal activity of alpha-hederin was confirmed, as was the minimal inhibitory concentration (25 micrograms ml-1).
Asclepias curassavica and Lactuca sativa latex saps inhibit the growth of Candida albicans because they degrade a great number of yeasts. This was confirmed by scanning and transmission electron microscopy observations. After a contact of 4 h and 6 h yeasts are deformed and emptied of their cytoplasmic content. Moreover, it appears that these saps, particularly Asclepias, also act on the cell wall: the substances presumed to be responsible for these effects were probably terpens and cardenolids but also enzymes, in particular glucanases.
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