Mycopathologia 116: 203-208, 1991. 9 1991 KluwerAcademic Publishers. Printed in the Netherlands. Clinical isolates of yeast produce a gliotoxin-like substance Darshana T. Shah & Bryan Larsen Departments of Microbiology, and Obstetrics & Gynecology, Marshall University School of Medicine, Huntington, WV 25755-9430, USA Received 3 January 1991; accepted in revised form 30 July 1991 Key words: Candida albicans, mycotoxin, gliotoxin, virulence Abstract Candida infections are major causes of morbidity in compromised human hosts, but our understanding of the virulence of Candida remains incomplete. The possibility that toxic fungal metabolites belonging to the chemical class epipolythiodioxopiperzine (ETP), which are reported to possess immunomodulating and antiphagocytic properties may be produced by Candida species was investigated. Reversed phase HPLC analysis of flash evaporated chloroform extracts of 7 day cultures of clinical Candida isolates grown in Minimal Essential Medium (MEM) with 5% fetal calf serum revealed the presence of a compound which eluted at the same time as the ETP, gliotoxin. Of 50 strains of yeast tested, 32 produced this gliotoxin-like material. This material was tested for other properties of ETP type toxins including the presence of mercaptans (Ellman reaction), ultraviolet absorbance spectrum and antibac- terial activity against Micrococcus lutea. These tests revealed gliotoxin-like material from yeast cultures to be similar to commercially supplied gliotoxin. This represents the first report of the presence of ETP- like compounds in yeast and raises the possibility that ETP's may contribute to the virulence of the organism. Introduction The incidence of infection in humans with patho- genic yeast such as Candida albicans has in- creased dramatically in the last two decades [1]. Although much of this increase has been found in immunocompromised hosts, where Candida in- fections are a major cause of morbidity and mor- tality, the role of specific virulence determinants in the intrinsic pathogenicity of Candida albicans still merits investigation. The virulence of this microorganism has been attributed to such prop- erties as attachment to tissue, invasion and toxi- genicity. Toxicity of Candida cell wall glyco- protein has been described [1]. Hydrolytic enzymes have been also implicated as virulence factors, and particular emphasis has been given to the extracellular acid proteases as well as phos- pholipases [2]. There are, however, conflicting reports on the relative importance of these en- zymes [3]. Yeast to mycelial phase conversion is also considered one of the factors contributing to pathogenicity [4]. In vitro investigations have indicated that mycelial cells release a product that selectively inhibits the human neutrophil function [5]. Toxins of Candida albicans have been claimed to be responsible for pathogenicity [6]; however, to date no such endo- or exotoxin has