Effects of polyoxin AL on cellular development inWangiella dermatitidis

WdChs1p, a class II chitin synthase, is more responsible than WdChs2p (Class I) for normal yeast reproductive growth in the polymorphic, pathogenic fungus Wangiella (Exophiala) dermatitidis

“…5a; see also Figs. 4a,b,5,6,7 of references Cooper et al 1984;Grove et al 1973, respectively), the septal regions of budding wdchs1Δ-A cells were not only broader sometimes, but also had cell walls that were thicker and septa devoid of clearly defined primary and secondary layers (Fig. 5b-d) or that were sometimes even absent, which produced cells that were multinucleate (Fig.…”

“…In contrast, total chitin synthase activity is drastically reduced in strains of the same three species devoid of their functional class I isozymes (Cabib et al 1989;Gow et al 1994;Wang et al 2001). Furthermore, and also in the manner of chs2 disruption mutants of S. cerevisiae and the lack of expression of CaChs1p in conditional mutants of C. albicans (Munro et al 2001;Shaw et al 1991;Schmidt et al 2002), wdchs1Δ cells are occasionally larger and frequently show septal region abnormalities that are not found in mutants with a defective class I isozyme or the wild type, such as failing to separate, showing septa that lack clearly defined primary and secondary septa that are reminiscent of those observed in TEM profiles of W. dermatitidis treated with the chitin synthase inhibitor polyoxin (Cooper et al 1984) and sometimes having abnormally broad mother cell-daughter bud necks and not forming even a defective septum between daughter nuclei. Finally, similar to the wdchs1Δwdchs2Δ double mutants of W. dermatitidis, chs1chs2 double mutants of S. cerevisiae also have more abnormal and exaggerated morphologies than their single parental chs mutant strains, although in the case of the latter the loss of function of both its class I and class II isozymes in the same background is much less severe and, to our knowledge, does not lead to lethality at any temperature (Shaw et al 1991).…”

“…Procedures for staining of the cell wall with Calcofluor (Sigma) and for the staining of nuclei with DAPI (4′,6′-diamide-2-phenylendole; Accurate Chemical), as well as those for transmission electron microscopy, have also been described (Cooper et al 1984;Ye and Szaniszlo 2000).…”

“…For example, chitin is a relatively minor component in yeast cells where it is localized primarily in septal regions (Cooper et al 1984;Szaniszlo and Momany 1993). In contrast, hyphae and sclerotic bodies, which are the two main alternative vegetative morphotypes of W. dermatitidis, not only have chitin in their septal regions, but also have considerable additional chitin in other cell wall areas (Szaniszlo et al 1983;Cooper et al 1984;Jacobs et al 1985;Harris and Szaniszlo 1986;McIntosh 1996).…”

Compounds active against cell walls of medically important fungi

“…By using the polyoxin complex AL (a crude mixture of polyoxins) on the polymorphic phaeohyphomycosis fungus Wangiella dermatitidis, morphologic effects similar to those described with treated cultures of both Coccidioides immitis and C. albicans were obtained (59). Treatment of wild-type yeast cells by the drug complex was found to cause irregular budding and defective septum formation.…”