Examination of Candida albicans strains from South Africa for the production of gliotoxin and other cytotoxic secondary metabolites

Abstract

Candida species cause superficial mycosis and more serious systemic infections. The virulence factors of Candida are their adherence and hyphae formation ability and the production of hydrolytic enzymes. In addition, they produce secondary metabolites which are also implicated in the pathogenesis. Literature on the production of gliotoxin, one of the metabolites by Candida spp. is controversial. The aim of this study was to examine production of gliotoxin and related secondary metabolites by C. albicans strains isolated from the oral cavities of patients with oral infections. Seventeen strains of Candida albicans were obtained and were grown in Eagle's minimal essential medium supplemented with 10% glucose and 5% foetal bovine serum for 10 and 30 days. Extraction of culture fluids and biomass was done using dichloromethane and examined using a two dimensional thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) with time of flight mass spectrometry (MS). Fifteen strains of C. albicans (88%) produced secondary metabolites with a molecular weight of 452 which was nearest to that of gliotoxin standard with a molecular weight of 326. Three major metabolites were isolated and identified. They were eburicol produced by 10 strains, Tryptophol produced by 10 strains and dehydro eburical produced by 12 strains of C. albicans. In conclusion, the strains of C. albicans isolated from the patients with oral infections did not produce gliotoxin. However, they produced tryptophol which is known to be produced by C. albicans, and they also produced eburicol and dehydro eburical which are intermediate compounds in the metabolic pathways to ergosterol. Further research is required to establish their role in the pathogenesis of this organism.

Production and Identification of Secondary Metabolite Gliotoxin-Like Substance Using Clinical Isolates of Candida spp.

“…A study achieved by [45], which looked at C. albicans isolates obtained from the oral cavity of patients with oral thrush, revealed that all tested isolates of C. albicans were produced to GT at concentrations ranging between 0.02 and 1.5 µg/ml. But is contradictory to the study achieved by [26,46], which reported that there is no mycotoxin gliotoxin produced in culture medium using various clinically and commensal isolates of C. albicans, C. tropical, C. glabrata, C. kefyr, etc. The correlation between mycotoxin gliotoxin production and virulence in Candida spp.…”

Macrophages Maintain Epithelium Integrity by Limiting Fungal Product Absorption

“…Of note, gliotoxin was also found to be produced by Candida spp. , including Candida albicans , even though there are conflicting reports on this subject ( Bertling et al., 2010 ; Kosalec et al., 2008 ; Kupfahl et al., 2007 ; Shah and Larsen, 1991 ; Shah et al., 1995 ; Tshabalala et al., 2016 ). To investigate whether Mɸs can sense fungal metabolites present in the fluids absorbed by epithelial cells, we infused fungi-depleted C57BL/6J mice with a hypotonic solution containing or not containing gliotoxin ( Figure 6 A).…”

“…Indeed, this fungi metabolite was shown to induce apoptosis in epithelial cells (Upperman et al, 2003) and to be produced by both pathobionts and food spoilage fungi such as Penicillium chrysogenum (Ismaiel and Papenbrock, 2015;Lewis et al, 2005), which is abundant in the murine intestinal tract (Wheeler et al, 2016). Of note, gliotoxin was also found to be produced by Candida spp., including Candida albicans, even though there are ll OPEN ACCESS Cell 183, 411-428, October 15, 2020 419 Article conflicting reports on this subject (Bertling et al, 2010;Kosalec et al, 2008;Kupfahl et al, 2007;Shah and Larsen, 1991;Shah et al, 1995;Tshabalala et al, 2016). To investigate whether Mɸs can sense fungal metabolites present in the fluids absorbed by epithelial cells, we infused fungi-depleted C57BL/6J mice with a hypotonic solution containing or not containing gliotoxin (Figure 6A).…”

Roles of the macrophages in colon homeostasis

“…It should be noted that gliotoxin was also produced by Candida spp. including Candida albicans, although there are conflicting studies on this [32,33]. To determine whether Mφs can detect fungal metabolites in fluids taken up by epithelial cells, we infused fungus-depleted C57BL/6J mice with a hypotonic solution containing or not gliotoxin (Figure 3D, adapted from [20]).…”

“…En effet, il a été démontré que ce métabolite fongique induisait l'apoptose des cellules épithéliales [8] et pouvait être produit à la fois par des pathobiontes et des champignons d'altération des aliments tels que Penicillium chrysogenum [31], qui est abondant dans le tractus intestinal murin [26]. Il convient de noter que la gliotoxine était également produite par Candida spp., y compris Candida albicans, même s'il existe des études contradictoires à ce sujet [32,33]. Pour déterminer si les Mφ peuvent détecter les métabolites fongiques présents dans les fluides absorbés par les cellules épithéliales, nous avons infusé des souris C57BL/6J appauvries en champignons avec une solution hypotonique contenant ou non de la gliotoxine (Figure 3D, adapted from [20]).…”