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Spices are used extensively in Lebanon not only to flavour foods but also for their medicinal properties. To date, no data are available regarding the nature of the toxigenic fungal species that may contaminate these products at the marketing stage in this country. Eighty samples corresponding to 14 different types of spices were collected throughout Lebanon to characterize the Aspergillus section Flavi contaminating spices marketed in Lebanon and the toxigenic potential of these fungal species. Most fungal genera and species were identified as belonging to Aspergillus section Flavi. Aspergillus flavus was the most frequent species, representing almost 80% of the isolates. Although identified as A. flavus by molecular analysis, some strains displayed atypical morphological features. Seven strains of A. tamarii and one A. minisclerotigenes were also isolated. Analyses of toxigenic potential demonstrated that almost 80% of strains were able to produce mycotoxins, 47% produced aflatoxins, and 72% produced cyclopiazonic acid, alone or in combination with aflatoxins.

The Cytolethal Distending Toxin (CDT) is a bacterial genotoxin produced by pathogenic bacteria causing major foodborne diseases worldwide. CDT activates the DNA damage response and induces inflammatory signatures in host cells, but the precise relationship between these outcomes has not been addressed so far. Here, we show that the cellular proinflammatory response and senescence induced by CDT depend on the cytoplasmic DNA sensor cGAS through the recognition of micronuclei. Indeed, despite active cell cycle checkpoints and in contrast to other DNA damaging agents, cells exposed to CDT reach mitosis where they accumulate massive DNA damage, resulting in chromosome fragmentation and micronucleus formation in daughter cells. These phenotypes are observed with CDT from various origins and in cancer or normal cell lines. Thus, our results establish a direct link between CDT-induced DNA damage, genetic instability and the cellular inflammatory response that may be relevant in the context of natural infection associated to chronic inflammation or carcinogenesis.

International audience; The Cytolethal Distending Toxin (CDT) is produced by many Gram-negative pathogenic bacteria responsible for major foodborne diseases worldwide. CDT induces DNA damage and cell cycle arrest in host-cells, eventually leading to senescence or apoptosis. According to structural and sequence comparison, the catalytic subunit CdtB is suggested to possess both nuclease and phosphatase activities, carried by a single catalytic site. However, the impact of each activity on cell-host toxicity is yet to be characterized. Here, we analyze the consequences of cell exposure to different CDT mutated on key CdtB residues, focusing on cell viability, cell cycle defects, and DNA damage induction. A first class of mutant, devoid of any activity, targets putative catalytic (H160A), metal binding (D273R), and DNA binding residues (R117A-R144A-N201A). The second class of mutants (A163R, F156-T158, and the newly identified G114T), which gathers mutations on residues potentially involved in lipid substrate binding, has only partially lost its toxic effects. However, their defects are alleviated when CdtB is artificially introduced inside cells, except for the F156-T158 double mutant that is defective in nuclear addressing. Therefore, our data reveal that CDT toxicity is mainly correlated to CdtB nuclease activity, whereas phosphatase activity may probably be involved in CdtB intracellular trafficking.

The Cytolethal Distending Toxin (CDT) is a bacterial genotoxin that activates the DNA damage response and induces inflammatory signatures in host cells, but the precise relationship between these outcomes has not been addressed so far. CDT induces a singular time-dependent increase of DNA damage and cell cycle defects, questioning on possible impaired response to this toxin over the cell cycle. Here, we identify mitosis as a crucial phase during CDT intoxination. Despite active cell cycle checkpoints and in contrast to other DNA damaging agents, CDT-exposed cells reach mitosis where they accumulate massive DNA damage, resulting in chromosome fragmentation and micronucleus formation. These micronuclei are recognized by cGAS that elicits an inflammatory signature resulting in cell distention and senescence. Our results unravel for the first time the mitotic consequences of CDT genotoxic activity and relate them to pro-inflammatory cellular response. These findings may have important implications during bacterial infection regarding CDT-mediated immunomodulatory and tumorigenic processes.

Contamination of foods with mycotoxins represents an important limit to the income of farmers and a major public health concern especially in tropical countries. Cassava represents an important part of the diet of many people in this part of the word and the most important smallholder crop in Africa. Fungal contamination of cassava products can occur at pre-harvest level or after, during processing, according to the conditions (moisture, temperature, competition with other microorganisms). Such fungal contamination can also lead to mycotoxin accumulation. The most common fungi found in cassava products belong to genera Rhyzopus, Aspergillus, Fusarium, Phoma and Penicillium. Their corresponding mycotoxins could also be found in cassava. However, until now, the correlation between the presence of Aspergillus flavus and its toxins aflatoxins remains unclear. In this review, we broadly report data about mycotoxins contamination of cassava (Manihot esculenta Crantz) and its derivatives, with a special emphasis on aflatoxins.