Synergy of lysozyme and lanoconazole on the morphology of Candida albicans

Synergism of lysozyme with the imidazole antifungal lanoconazole (LCZ) has been demonstrated in vitro against Candida albicans. To determine the mechanism of the synergistic action, the effects of subinhibitory concentrations of lysozyme (50 microg ml(-1)) and LCZ (1.25 microg ml(-1)), used alone and in combination, on the morphology and ultrastructure of C. albicans cells were studied by fluorescence microscopy using Fungiflora Y, as well as by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In the presence of lysozyme, the separation of apparently mature cells from each other was inhibited, and cells in which cell wall-like material had markedly accumulated in the periplasmic space were frequently observed. Such intracellular ultrastructural changes were not seen in LCZ-treated cells, but normal septal wall biogenesis was inhibited with the resultant formation of long chains of interconnecting cells. When the cultures were treated with the combination of lysozyme and LCZ, intracellular accumulation of cell wall-like materials increased in extent, and the peripheral wall structure was severely damaged. These morphological and ultrastructural findings lead us to the following conclusions: (1) lysozyme and LCZ inhibit the process of cell division in different manners; (2) lysozyme appears to affect cell wall formation more directly and drastically by interrupting the normal assembly and integration of cell wall components; and (3) these effects of lysozyme are noticeably enhanced when combined with LCZ.