A morphological susceptibility assay to rank pneumocandin analogs against Aspergillus sp.

M.B.KURTZ, J.MARRINAN, J.ONISHI, S.DREIKORN, I.B.HEATH and C.DOUGLAS.

Abstract: 

A broth microdilution susceptibility assay developed to rank the activity of pneumocandin analogs against Aspergillus species will be described. The assay is based on the profound morphological effects produced by the echinocandin-like class of compounds. Germ tubes of treated fungi are thicker and more highly branched than control hyphae; drug-treated hyphal tips are swollen and distended. The assay endpoint is the lowest concentration required to produce the morphological effect and is called MEC (minimum effective concentration). MEC determinations made microscopically corresponded to effects determined by visual inspection of growth in microtiter plates. Electron micrographs of drug-treated germlings of Aspergillus showed very stubby growth, with thick walls and a conspicuous dark outer layer, which was much thicker in the sub-apical regions. Tips showed small Spitzenkorpers and few wall vesicles but more or less normal numbers of Golgi body equivalents. Septa were more frequent and formed much shorter hyphal compartments than controls. The relevance of the MEC assay to activity in in vivo models for systemic aspergillosis will be discussed. The gross morphological changes and the potent inhibition of 1,3-beta-D-glucan biosynthesis in cell free extracts from Aspergillus are consistent with inhibition of glucan synthesis as the primary mode of action of these inhibitors against Aspergillus as well as Candida species.
1993

abstract No: 

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Full conference title: 

ICAAC 33rd, 1993
    • ICAAC 33rd