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Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
Very recently, the concept of regulation of mycotoxin biosynthesis through chromatin modification was further, corroborated, again with the A. nidulans sterigmatocystin biosynthesis genes as proof of principle. The stc gene cluster is silent during normal growth and occupied and elevated levels of heterochromatin protein A (HepA), while a decrease of HepA marks is associated with the onset of sterigmatocystin synthesis. A heap deletion mutant showed strongly increased transcript levels for the biosynthesis genes of sterigmatocystin, penicillin, and terrequinone A, the genes of the AflR regulator and, interestingly, LaeA.198 ClrD is a histone methyltransferase which trimethylates the lysine residue 9 in history H3. ClrD activity is a prerequisite for efficient HepA labeling as HepA binding requires trimethylation. Consistent with the model, the same study presents a clrD mutant, which showed increased stc gene transcription and somewhat higher sterigmatocystin titers. The authors conclude that LaeA counteracts trimethylation at natural product gene loci which then leads to decreased HepA binding and, thus, prevents formation of repressive facultative heterochromatin. LaeA-mediated pleiotropic transcriptional regulation has been found outside the genus Aspergillus as well. Kosalková et al.199 identified an orthologous gene in P. chrysogenum, the producer of penicillin and the mycotoxin roquefortin C. Homologous overexpression of LaeA under the control of the A. awamori glutamate dehydrogenase promoter increased penicillin yields by 25% calculated as benzylpenicillin per mg dry weight. Attenuation of laeA transcription by RNAi decreased penicillin titers by more than 50%. RNAi also impacted upon conidial pigmentation and morphological differentiation, as conidia are colorless and their overall amount reduced by 50%. Roquefortin C production remained unaffected after these genetic manipulations, indicating an LaeA-independent regulation of its biosynthesis.
Settled dust assessment in clinical environment: useful for the evaluation of a wider bioburden spectrum
Published in International Journal of Environmental Health Research, 2021
Carla Viegas, Beatriz Almeida, Ana Monteiro, Inês Paciência, João Cavaleiro Rufo, Elisabete Carolino, Anita Quintal-Gomes, Magdalena Twarużek, Robert Kosicki, Geneviéve Marchand, Liliana Aranha Caetano, Susana Viegas
The presence of mycotoxins in clinical environments is not desirable since it represents an additional health risk factor for patients and workers. Unfortunately, mycotoxins are not commonly analyzed in samples from health care facilities and only one previous report has already reported mycotoxins data (Heutte et al. 2017). No correlations were found between mycotoxins contamination and specific cleaning routines, or other aspects able to explain the findings, since these were similar among all the assessed PHCC. In addition, no correlation was observed between total fungal load and mycotoxins levels. Similar to our findings, sterigmatocystin was already detected in a health care facility in 3 samples of bioaerosols at levels of 0.31, 0.32, and 1.45 μg per m3 (Heutte et al. 2017). Although in a different matrix the values found were lower than the one found in our study. According to IARC classification, sterigmatocystin is a possible human carcinogen (2B) and show immunotoxic and immunomodulatory activity, together with mutagenic effects (McConnell and Garner 1994; Liu et al. 2014; Gao et al. 2015; Viegas et al. 2018d). The conclusion made by EFSA Panel on Contaminants in the Food Chain (CONTAM) (2013) was that the genotoxicity of sterigmatocystin is based on the formation of DNA adducts that, if unrepaired, increase the likelihood of mutation fixation (Viegas et al. 2018d).