Effects of Hexose Analogues on Fungi: Mechanisms of Ingibition and of Resistance

Abstract

I. SUMMARY Although the effects of a number of sugar analogues are discussed in this review, most attention is devoted to 2‐deoxy‐D‐glucose (deGlc) and L‐sorbose. The growth of fungi is not uniformly inhibited by sugar analogues since some species or strains can metabolize sugars which severely inhibit others. Sugar analogues usually cause inhibitions by being used in metabolism in place of glucose. Both deGlc and sorbose are metabolized by several species but, in general, only a small fraction of the analogue is utilized. The uptake and phosphorylation of readily metabolized sugars are inhibited by deGlc. Inhibitions by sugar analogues occur on media containing non‐carbohydrate sources of carbon, so inhibition of sugar uptake is unlikely to be a major component of the growth inhibition which occurs on sugar‐containing media. Hexokinase phosphorylates deGlc, and its 6‐phosphate inhibits the activity of especially phosphohexose isomerase and glucose 6‐phosphate dehydrogenase. Apart from an involvement in synthesis of more complex sugars, formation of deGlc‐6P is the usual limit of metabolism of this sugar analogue. Accumulation of the phosphate ester leads to a considerable drain on phosphate pools and ATP levels decline drastically. Indeed, deGlc rapidly initiates degradation of purine nucleotides which can proceed at least to the level of hypoxanthine. In Saccharomyces cerevisiae, deGlc can be condensed to dideoxytrehalose and, in most fungi, polysaccharide synthesis is affected. Preformed wall material is eroded and synthesis of new wall components is prevented by sequestering of uridine and guanosine nucleotides through reaction with deGlc. Interference with the structure of the wall greatly reduces osmotic stability, and cell lysis is the major cause of inhibition of growth by deGlc in yeasts and filamentous fungi alike. L‐Sorbose is not phosphorylated, and the biochemical basis of the inhibitions caused by this analogue is obscure. Some enzymes involved in polysaccharide synthesis are sensitive to inhibition by sorbose, and a characteristic of growth on this sugar is formation of an abnormally thick cell wall. Filamentous fungi grown on solid medium containing sorbose assume an abnormal growth form in which cells are much shortened and branching frequency is increased. There are indications that sorbose, perhaps by interfering with cell wall structure, affects hyphal morphogenesis and that this effect may be magnified into a macroscopic change in the characteristics of the colony during growth on solid medium by secondary environmental effects. Mutants, resistant to deGlc, have alterations in either transport, hexokinase or phosphatase functions, thus emphasizing the important of accumulation of deGlc‐6P in the inhibitions caused by this analogue. Generalization is less easy about mutants resistant to sorbose. The majority are defective in transport, but others show defects in phosphoglucomutase and polysaccharide synthases and there are some correlations with morphological changes which underline the involv...

Germination triggers of Metarhizium anisopliae conidia are related to host species

“…It is tempting, therefore, to speculate that the toxic effect of dGlc on strain 549 and its ability to germinate rapidly on glucose are linked, presumably because dGlc is being used in metabolism in place of glucose. It is well established that dGlcPO, weakens the cell wall of yeasts by adversely affecting the incorporation of glucose into wall polysaccharides (Moore, 1981). Microscopic examination of strain 549 revealed no evidence for lysis of hyphal tip cells.…”

“…cerevisiae (Zimmermann & Scheel, 1977) and filamentous fungi (Moore, 1981 ;Allen e t al., 1989;Kirimura e t al., 1992). These mutants display pleiotropic alterations in enzymes that are normally glucose-repressible.…”

“…As strains 549 and 808 differed in their ability to germinate rapidly on glucose, we tested well-characterized glucose analogues (Eraso & Gancedo, 1985;Moore, 1981) that are phosphorylated but not extensively metabolized (e.g. dGlc) and sugars that can only be transported into the cell (6-deoxyglucose and 3-0-methylglucose) to determine to what extent a sugar should be metabolized to allow germination and catabolite repression.…”

The Barley mlo-gene: an important powdery mildew resistance source

“…The glucose analogue DDG is described as a powerful inhibitor of callose formation in vivo [25] but it does not inhibit activity of the callose synthase enzyme in vitro [37,39]. However, the effects of DDG, and another glucose analogue mannose [37], may well be indirect since both are known to sequester plant cell phosphate [18,20,38]. Phosphate sequestration would reduce the plant cells potential to synthesise the ATP needed for vital phosphorylation reactions during energy metabolism [23,56].…”

Mycelial growth of strains of Pleurotus ostreatus developed on agar and its correlation with the productivity in pilot production farm

“…The main aspects involved in the inhibition of cell metabolism by 2-DG are interference with sugar uptake, inhibition of hexokinase and inhibition of phosphoglucose isomerase. Other enzymes involved in different stages of glycolysis and in other pathways of the cell metabolism are also likely to be inhibited by 2-DG-6-phosphate (8). 2-DG has often been used to select mutant microorganisms derepressed for sugars metabolism (7,11,14).…”