Diplonine, a Neurotoxin Isolated from Cultures of the Fungus Stenocarpella maydis (Berk.) Sacc. that Induces Diplodiosis

Abstract

Diplodiosis is a neuromycotoxicosis of cattle and sheep caused by ingestion of maize infected with the ear-rot fungus Stenocarpella (= Diplodia) maydis. Apart from ataxia, paresis and paralysis, the toxin is responsible for stillbirths and neonatal losses characterized by the presence of spongiform degeneration in the white matter of the brain in the offspring of dams exposed to infected maize cobs. In the present study a toxin, named diplonine, which induced neurological signs in guinea pigs resembling some of those occurring in cattle and sheep, was isolated from S. maydis cultures. Purification of diplonine was achieved by methanol extraction followed by chromatographic separation on silica gel and RP-18 stationary phases. The structure and relative configuration of diplonine was defined by analysis of NMR and MS data as (S)-2-amino-2-[(1R,2S)-1-hydroxy-2-methylcyclopropyl]acetic acid or the (S)-2-amino-2-[(1S,2R)-diastereomer.

Nodding syndrome in Mundri county, South Sudan: Environmental, nutritional and infectious factors

“…One is diplodiosis, a neurotoxic condition of cattle and sheep in southern Africa caused by ingestion of maize ears contaminated with Stenocarpella maydis, which elaborates diplonine. 72 Clinical signs, which appear after 2-5 days and disappear later, include: reluctance to move, a wide-based stance and a stiff-legged highstepping gait, repeated falling, paresis/paralysis, constipation and salivation. The second is Aspergillus clavatus, which is associated with a fatal tremorgenic syndrome of cattle in Africa 73 and elsewhere.…”

Effects of Stenocarpella maydis in seeds and in the initial development of corn

“…The rot of ears can cause reduction in yield and quality of harvested grains. It is also known that this fungus produces toxin, which affects the economic and nutritional value of the product (Krout-Greenberg et al, 2013;Snyman et al, 2011;Casa et al, 2006).…”

Characterization of cell death caused by diplodiatoxin and dipmatol, toxic metabolites of Stenocarpella maydis

“…Previously, in vivo models were used to investigate the toxicity of the three S. maydis metabolites i.e. diplodiatoxin, dipmatol and diplonine ( Ackerman et al, 1995, Rao et al, 2003, Snyman et al, 2011and Steyn et al, 1972. In rats, diplodiatoxin was reported to cause liver damage (i.e.…”

“…increased alkaline and acid phosphatase, as well as aspartate and alanine aminotransferase activities) and inhibition of the brain acetylcholinesterase activity (Rao et al, 2003). There is a dearth of information on the in vivo toxicity of dipmatol and diplonine, except that the toxicity of dipmatol was evaluated in broiler chickens ( Ackerman et al, 1995) and guinea pigs dosed with diplonine (1580 mg/kg body weight) exhibited clinical signs akin to the neurological signs observed in ruminants suffering from diplodiosis (Snyman et al, 2011). Hence, the mechanism of action of the currently known S. maydis metabolites is poorly understood.…”

“…To date, different metabolites (i.e. diplodiatoxin, dipmatol, chaetoglobosins and diplonine) have been isolated from S. maydis-contaminated cultures ( Ackerman et al, 1995, Rogers et al, 2014, Snyman et al, 2011and Steyn et al, 1972. A major drawback is that none of these S. maydis metabolites isolated thus far have been administered to ruminants in an attempt to reproduce diplodiosis.…”