Effect of mycolase and amphotericin B on Candida albicans and Candida pseudotropicalis in vitro and in vivo.

Abstract

A mixture of enzymes (mycolase) capable of lysing yeast cell walls was prepared from culture filtrates of Physarum polycephalum. The enzymes present in mycolase included chitinase, beta-1,3-glucanases and exo-glycosidases. The pH optima of these enzymes were in the range 3.5-5.0 and they had low activities at pH 7.0. Mycolase produced spheroplasts from Candida pseudotropicalis and, unlike commercial enzyme preparations such as L1, chitinase, beta, 1,3-glucanase and beta-glucosidase, had some candicidal activity in vitro against C. pseudotropicalis and C. albicans. Mycolase potentiated the antifungal activity of amphotericin B against C. pseudotropicalis grown in shake flask culture but did not potentiate the antifungal activity of the antibiotic against similar cultures of C. albicans; indeed antagonism between mycolase and amphotericin B was sometimes observed with the latter yeast. Mycolase caused an approximately two-fold increase in the total and viable counts of cultures of C. albicans inoculated with stationary phase cells. These increases, which were observed within about 30 min, were attributed to mycolase inducing the premature release of viable buds from 'lag' phase cells. Mycolase also increased the rate at which C. albicans formed germ tubes when the yeast was cultured in a medium containing serum. Mycolase alone or in combination with amphotericin B did not appreciably enhance phagocytosis or intracellular killing of the yeasts by unstimulated mouse peritoneal macrophages. Studies on mice infected systemically with C. albicans showed that mycolase only slightly enhanced amphotericin B therapy.