Ma L, Salas O, Bowler K, Oren-Young L, Bar-Peled M, Sharon A

Mol Plant Pathol. 2016 Mar 17

Botrytis cinerea is a model plant pathogenic fungus that causes grey mold and rot diseases in a wide range of agriculturally important crops. A previous study identified two enzymes and corresponding genes (bcdh, bcer) that are involved in the biochemical transformation of UDP-glucose, the major fungal wall nucleotide sugar precursor, to UDP-rhamnose. We report here that deletion of bcdh, the first biosynthetic gene in the metabolic pathway, or of bcer, the second gene in the pathway, abolished production of rhamnose-containing glycans in these mutant strains. Deletion of bcdh or double deletion of both bcdh and bcer had no apparent effect on fungal development or pathogenicity. Interestingly, deletion of the bcer gene alone adversely affected fungal development, giving rise to altered hyphal growth and morphology, as well as reduced sporulation, sclerotia production, and virulence. Treatments with wall stressors suggested alteration of cell wall integrity. Analysis of nucleotide-sugars revealedaccumulation of the UDP-rhamnose pathway intermediate UDP-4-keto-6-deoxy-glucose (UDP-KDG) in hyphae of the Δbcer strain. UDP-KDGcould not be detected in hyphae of the wild type strain, indicating fast conversion to UDP-rhamnose by the BcEr enzyme. The correlation between high UDP-KDG, modified cell wall, and developmental defects, raises the possibility that high levels of UDP-KDG result in deleterious effects on cell wall composition and hence on virulence. This is the first report demonstrating that accumulation of a minor nucleotide-sugar intermediate has such a profound and adverse effects on a fungus. The ability to identify molecules that inhibit Er (also known as NRS/ER) enzymes or mimic UDP-KDG might lead to development of new antifungal drugs