Toxic C17-Sphinganine Analogue Mycotoxin, Contaminating Tunisian Mussels, Causes Flaccid Paralysis in Rodents

Abstract

Severe toxicity was detected in mussels from Bizerte Lagoon (Northern Tunisia) using routine mouse bioassays for detecting diarrheic and paralytic toxins not associated to classical phytoplankton blooming. The atypical toxicity was characterized by rapid mouse death. The aim of the present work was to understand the basis of such toxicity. Bioassay-guided chromatographic separation and mass spectrometry were used to detect and characterize the fraction responsible for mussels’ toxicity. Only a C17-sphinganine analog mycotoxin (C17-SAMT), with a molecular mass of 287.289 Da, was found in contaminated shellfish. The doses of C17-SAMT that were lethal to 50% of mice were 750 and 150 μg/kg following intraperitoneal and intracerebroventricular injections, respectively, and 900 μg/kg following oral administration. The macroscopic general aspect of cultures and the morphological characteristics of the strains isolated from mussels revealed that the toxicity episodes were associated to the presence of marine microfungi (Fusarium sp., Aspergillus sp. and Trichoderma sp.) in contaminated samples. The major in vivo effect of C17-SAMT on the mouse neuromuscular system was a dose- and time-dependent decrease of compound muscle action potential amplitude and an increased excitability threshold. In vitro, C17-SAMT caused a dose- and time-dependent block of directly- and indirectly-elicited isometric contraction of isolated mouse hemidiaphragms.

Elucidating the Diversity of Aquatic Microdochium and Trichoderma Species and Their Activity against the Fish Pathogen Saprolegnia diclina

“…Even though Trichoderma species are commonly considered beneficial fungi, some Trichoderma strains, including T. harzianum , Trichoderma koningii , Trichoderma longibrachiatum , Trichoderma pseudokoningii and Trichoderma viride , maybe pathogenic to human [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. Some marine Trichoderma were associated to contaminated mussels and some were even toxic to aquatic animals, such as Artemia larvae [ 25 , 88 ]. Therefore, evaluations of the adverse effects of our Trichoderma isolates on the environment and humans are needed.…”

Bioactive Compounds Produced by Strains of Penicillium and Talaromyces of Marine Origin

“…The issue of bioactive compound production is fundamental in understanding the complex ecological relationships established among and between sea-inhabiting organisms and microorganisms, and presents human nutritional implications due to the possibility that such fungal strains contaminate sea food, and their metabolites eventually act as mycotoxins [ 4 , 5 ]. However, the pharmaceutical industry can be regarded as the application field where products from marine fungi have the most substantial impact, since many of them have entered the clinical pipeline in view of being exploited as novel drugs.…”

Purification, Toxicity and Functional Characterization of a New Proteinaceous Mussel Biotoxin from Bizerte Lagoon

“…Analyses made on contaminated mussel samples, i.e., positive Diarrheic Shellfish Poisoning (DSP) toxin test, revealed the absence of known marine biotoxins, as well as no relation between episodes of toxicity and harmful algal blooms [21], which suggests that mussel toxicity may be due to new toxin(s). Two fractions responsible for mussel toxicity were isolated using the bio-guided chromatographic separation technique.…”

“…Two fractions responsible for mussel toxicity were isolated using the bio-guided chromatographic separation technique. LC-MS analyzes showed that the less retained fraction, identified and characterized by Marrouchi et al [21] and named C17-sphinganine analogue mycotoxin (C17-SAMT), has a molecular mass of 287,289 Da. The major effect of C17-SAMT on the mouse neuromuscular system in vivo was a dose-and time-dependent decrease of the compound muscle action potential amplitude and an increased excitability threshold.…”