Thioridazine inhibits gene expression control of the cell wall signaling pathway (CWI) in the human pathogenic fungus Paracoccidioides brasiliensis

2016 ◽  
Vol 291 (3) ◽  
pp. 1347-1362 ◽  
Author(s):  
Daniela Leite Jabes ◽  
Ana Claudia de Freitas Oliveira ◽  
Valquíria Campos Alencar ◽  
Fabiano Bezerra Menegidio ◽  
Débora Liliane Souza Reno ◽  
...  
2021 ◽  
Author(s):  
David Aciole Barbosa ◽  
Alexandre Santos Simeone ◽  
Ana Carolina Humberto ◽  
Yara Natercia Lima Faustino de Maria ◽  
Regina Costa de Oliveira ◽  
...  

Abstract Previous genomic/transcriptomic analyses of Talaromyces marneffei (TM) unravelled relevant pathogenicity-related elements, as well as chromosomal regions potentially involved with the production of non-coding RNAs (ncRNAs), which have been parsimoniously reported in fungi. This manuscript describes a comprehensive pan-transcriptome assembly for TM that identifies a series of previously undetected genetic elements in this emerging pathogenic fungus. Our results confirm that ~58.28% of the 9,480 genes currently annotated in the TM genome are, in fact, transcribed in vivo and that ~23.6% of them may display alternative isomorphs. Moreover, we identified 585 transcripts that do not match any gene currently mapped in the genome, represented by 90 coding transcripts and 140 ncRNAs, including 48 long non-coding RNAs (lncRNAs). Overall, we expect that the novel elements described herein may contribute to improve the currently available Talaromyces databases and foster studies aiming at characterizing lncRNA-mediated gene expression control in fungi.


2021 ◽  
Vol 7 (4) ◽  
pp. 272
Author(s):  
Felicia Adelina Stanford ◽  
Nina Matthias ◽  
Zoltán Cseresnyés ◽  
Marc Thilo Figge ◽  
Mohamed I. Abdelwahab Hassan ◽  
...  

Iron is an essential micronutrient for most organisms and fungi are no exception. Iron uptake by fungi is facilitated by receptor-mediated internalization of siderophores, heme and reductive iron assimilation (RIA). The RIA employs three protein groups: (i) the ferric reductases (Fre5 proteins), (ii) the multicopper ferroxidases (Fet3) and (iii) the high-affinity iron permeases (Ftr1). Phenotyping under different iron concentrations revealed detrimental effects on spore swelling and hyphal formation under iron depletion, but yeast-like morphology under iron excess. Since access to iron is limited during pathogenesis, pathogens are placed under stress due to nutrient limitations. To combat this, gene duplication and differential gene expression of key iron uptake genes are utilized to acquire iron against the deleterious effects of iron depletion. In the genome of the human pathogenic fungus L. corymbifera, three, four and three copies were identified for FRE5, FTR1 and FET3 genes, respectively. As in other fungi, FET3 and FTR1 are syntenic and co-expressed in L. corymbifera. Expression of FRE5, FTR1 and FET3 genes is highly up-regulated during iron limitation (Fe-), but lower during iron excess (Fe+). Fe- dependent upregulation of gene expression takes place in LcFRE5 II and III, LcFTR1 I and II, as well as LcFET3 I and II suggesting a functional role in pathogenesis. The syntenic LcFTR1 I–LcFET3 I gene pair is co-expressed during germination, whereas LcFTR1 II- LcFET3 II is co-expressed during hyphal proliferation. LcFTR1 I, II and IV were overexpressed in Saccharomyces cerevisiae to represent high and moderate expression of intracellular transport of Fe3+, respectively. Challenge of macrophages with the yeast mutants revealed no obvious role for LcFTR1 I, but possible functions of LcFTR1 II and IVs in recognition by macrophages. RIA expression pattern was used for a new model of interaction between L. corymbifera and macrophages.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.


Nature ◽  
2011 ◽  
Vol 473 (7347) ◽  
pp. 337-342 ◽  
Author(s):  
Björn Schwanhäusser ◽  
Dorothea Busse ◽  
Na Li ◽  
Gunnar Dittmar ◽  
Johannes Schuchhardt ◽  
...  

2004 ◽  
Vol 22 (7) ◽  
pp. 824-826 ◽  
Author(s):  
Francine B Perler

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