Bacterial Enrichment Cultures Biotransform the Mycotoxin Deoxynivalenol into a Novel Metabolite Toxic to Plant and Porcine Cells.

The mycotoxin deoxynivalenol (DON), produced in wheat, barley and maize by Fusarium graminearum and Fusarium culmorum, is threatening the health of humans and animals. With its worldwide high incidence in food and feed, mitigation strategies are needed to detoxify DON, maintaining the nutritional value and palatability of decontaminated commodities. A promising technique is biological degradation, where microorganisms are used to biotransform mycotoxins into less toxic metabolites. In this study, bacterial enrichment cultures were screened for their DON detoxification potential, where DON and its potential derivatives were monitored. The residual phytotoxicity was determined through a bioassay using the aquatic plant Lemna minor L. Two bacterial enrichment cultures were found to biotransform DON into a still highly toxic metabolite for plants. Furthermore, a cytotoxic effect was observed on the cellular viability of intestinal porcine epithelial cells. Through liquid chromatography high-resolution mass spectrometry analysis, an unknown compound was detected, and tentatively characterized with a molecular weight of 30.0 Da (i.e., CH2O) higher than DON. Metabarcoding of the subsequently enriched bacterial communities revealed a shift towards the genera Sphingopyxis, Pseudoxanthomonas, Ochrobactrum and Pseudarthrobacter. This work describes the discovery of a novel bacterial DON-derived metabolite, toxic to plant and porcine cells.

Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing.

In order to adequately evaluate the clinical relevance of genetic testing in sporadic breast and ovarian cancer patients, we offered comprehensive BRCA1/2 mutation analysis in patients without a family history for the disease. We evaluated the complete coding and splice site regions of BRCA1/2 in 193 sporadic patients. In addition, a de novo mutation was further investigated with ultra deep sequencing and microsatellite marker analysis. In 17 patients (8.8%), a deleterious germline BRCA1/2 mutation was identified. The highest mutation detection ratio (3/7 = 42.9%) was obtained in sporadic patients diagnosed with breast and ovarian cancer after the age of 40. In 21 bilateral breast cancer patients, two mutations were identified (9.5%). Furthermore, 140 sporadic patients with unilateral breast cancer were investigated. Mutations were only identified in patients diagnosed with breast cancer before the age of 40 (12/128 = 9.4% vs. 0/12 with Dx > 40). No mutations were detected in 17 sporadic male breast cancer and 6 ovarian cancer patients. BRCA1 c.3494_3495delTT was identified in a patient diagnosed with breast and ovarian cancer at the age of 52 and 53, respectively, and was proven to have occurred de novo at the paternal allele. Our study shows that the mutation detection probability in specific patient subsets can be significant, therefore mutation analysis should be considered in sporadic patients. As a consequence, a family history for the disease and an early age of onset should not be used as the only criteria for mutation analysis of BRCA1/2. The relatively high mutation detection ratio suggests that the prevalence of BRCA1/2 may be underestimated, especially in sporadic patients who developed breast and ovarian cancer. In addition, although rare, the possibility of a de novo occurrence in a sporadic patient should be considered.