A Study of the Fungistatic and Fungicidal Properties and of the Toxicity for Mice of Sodium Azide

Abstract

The inhibitory action of sodium azide (NaN8) on the growth of bacteria was first reported by Schattenfroh (1896). Apparently no further work of this nature was published until 1937. In the past few years several contributions have appeared dealing with the effects of NaN3 on microorganisms, but, so far as the writers can determine, these studies have not included the filamentous fungi. A familiarity with the influence of NaNs on several species of bacteria, together with the chance observation of its pronounced inhibitory effect on Penicillium notatum, led to an investigation of this compound as possible fungicide, and as a chemotherapeutic agent in fungous infections. Early experiments gave sufficiently striking results to warrant the publication of a preliminary report by Kempf and Nukngester (in press). The principal purpose of this article is to present additional experimental data relative to the fungistatic and fungicidal properties and the toxicity for mice of NaN3. In order to obtain data of broad mycological significance, the following group of organisms was studied. These species represent a wide taxonomic range as well as a great diversity of normal habitats. Mucor rhizopodiformis is a sapro-phytic phycomycete; Aspergillus niger and Pencillium notatum are common sap-rophytic ascomycetous molds; Stereum gausapatum, a basidiomycete, is the cause of a heart rot in hardwood trees. Alternaria solani, an imperfect fungus, is the etiological agent of a common blight of solanaceous plants. The remaining organisms, namely, Trichophytor gypseum,' Blastomyces dermatitis, Histoplasma capsulatum, and the yeast-like Monilia albicans, are all animal pathogens of the class Fungi Imperfecti. FUNGISTATIC ACTION The ability of NaN3 to inhibit the growth of fungi was determined by growing the test organisms in the presence of graded concentrations of the chemical. In certain preliminary experiments the NaN3 was incorporated in agar culture media and the organisms grown in petri dishes. Such a procedure was employed because of its simplicity. Two serious faults were soon appreciated and the method therefore abandoned. The most obvious difficulty was the lack of a simple criterion for determining the amount of growth. When cultured on solid media, it is commonly observed with fungi that various environmental factors, such as nutritive materials, hydrogen ion concentration and oxygen tension, may greatly 1 Culture No. 601, Trichophyton mentagrophytes (T. gypseum), of the U. S. Public Health Service, obtained through the courtesy of C. W. Emmons. 331