Gene silencing with RNA interference in the human pathogenic fungus

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.

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Deletion of pksA attenuates the melanogenesis, growth and sporulation ability and causes increased sensitivity to stress response and antifungal drugs in the human pathogenic fungus Fonsecaea monophora

Microbiological Research ◽

10.1016/j.micres.2020.126668 ◽

2021 ◽

Vol 244 ◽

pp. 126668

Author(s):

Xing Xiao ◽

Yu Li ◽

Yu Lan ◽

Jing Zhang ◽

Ya He ◽

...

Keyword(s):

Stress Response ◽

Pathogenic Fungus ◽

Antifungal Drugs ◽

Fonsecaea Monophora ◽

Increased Sensitivity ◽

Human Pathogenic Fungus

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Viroids as a Tool to Study RNA-Directed DNA Methylation in Plants

Cells ◽

10.3390/cells10051187 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1187

Author(s):

Michael Wassenegger ◽

Athanasios Dalakouras

Keyword(s):

Dna Methylation ◽

Rna Interference ◽

Gene Silencing ◽

Plant Cells ◽

Transcriptional Gene Silencing ◽

Rnai Machinery ◽

Double Stranded Rna ◽

Post Transcriptional Gene Silencing ◽

Cumulative Amount

Viroids are plant pathogenic, circular, non-coding, single-stranded RNAs (ssRNAs). Members of the Pospiviroidae family replicate in the nucleus of plant cells through double-stranded RNA (dsRNA) intermediates, thus triggering the host’s RNA interference (RNAi) machinery. In plants, the two RNAi pillars are Post-Transcriptional Gene Silencing (PTGS) and RNA-directed DNA Methylation (RdDM), and the latter has the potential to trigger Transcriptional Gene Silencing (TGS). Over the last three decades, the employment of viroid-based systems has immensely contributed to our understanding of both of these RNAi facets. In this review, we highlight the role of Pospiviroidae in the discovery of RdDM, expound the gradual elucidation through the years of the diverse array of RdDM’s mechanistic details and propose a revised RdDM model based on the cumulative amount of evidence from viroid and non-viroid systems.

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Recent Advances in the Development of Exogenous dsRNA for the Induction of RNA Interference in Cancer Therapy

Molecules ◽

10.3390/molecules26030701 ◽

2021 ◽

Vol 26 (3) ◽

pp. 701

Author(s):

Tatiana S. Golubeva ◽

Viktoria A. Cherenko ◽

Konstantin E. Orishchenko

Keyword(s):

Gene Expression ◽

Rna Interference ◽

Molecular Biology ◽

Gene Silencing ◽

Regulation Of Gene Expression ◽

Research Area ◽

Disease Treatment ◽

Practical Applications ◽

Agricultural Plants ◽

Insect Reproduction

Selective regulation of gene expression by means of RNA interference has revolutionized molecular biology. This approach is not only used in fundamental studies on the roles of particular genes in the functioning of various organisms, but also possesses practical applications. A variety of methods are being developed based on gene silencing using dsRNA—for protecting agricultural plants from various pathogens, controlling insect reproduction, and therapeutic techniques related to the oncological disease treatment. One of the main problems in this research area is the successful delivery of exogenous dsRNA into cells, as this can be greatly affected by the localization or origin of tumor. This overview is dedicated to describing the latest advances in the development of various transport agents for the delivery of dsRNA fragments for gene silencing, with an emphasis on cancer treatment.

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Comparative Genomics Suggests That the Human Pathogenic Fungus Pneumocystis jirovecii Acquired Obligate Biotrophy through Gene Loss

Genome Biology and Evolution ◽

10.1093/gbe/evu155 ◽

2014 ◽

Vol 6 (8) ◽

pp. 1938-1948 ◽

Cited By ~ 31

Author(s):

Ousmane H. Cissé ◽

Marco Pagni ◽

Philippe M. Hauser

Keyword(s):

Comparative Genomics ◽

Gene Loss ◽

Pathogenic Fungus ◽

Pneumocystis Jirovecii ◽

Human Pathogenic Fungus

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Immunosuppression in vitro by a metabolite of a human pathogenic fungus.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.81.12.3835 ◽

1984 ◽

Vol 81 (12) ◽

pp. 3835-3837 ◽

Cited By ~ 104

Author(s):

A. Mullbacher ◽

R. D. Eichner

Keyword(s):

Pathogenic Fungus ◽

Human Pathogenic Fungus

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What Are the Best Parents for Hybrid Progeny? An Investigation into the Human Pathogenic Fungus Cryptococcus

Journal of Fungi ◽

10.3390/jof7040299 ◽

2021 ◽

Vol 7 (4) ◽

pp. 299

Author(s):

Man You ◽

Jianping Xu

Keyword(s):

Pathogenic Fungus ◽

Sequence Divergence ◽

Hybrid Vigor ◽

Phenotypic Trait ◽

Hybrid Progeny ◽

Melanin Production ◽

Fluconazole Resistance ◽

Human Pathogenic Fungus ◽

Two Temperatures ◽

The Relationship

Hybridization between more divergent organisms is likely to generate progeny with more novel genetic interactions and genetic variations. However, the relationship between parental genetic divergence and progeny phenotypic variation remains largely unknown. Here, using strains of the human pathogenic Cryptococcus, we investigated the patterns of such a relationship. Twenty-two strains with up to 15% sequence divergence were mated. Progeny were genotyped at 16 loci. Parental strains and their progeny were phenotyped for growth ability at two temperatures, melanin production at seven conditions, and susceptibility to the antifungal drug fluconazole. We observed three patterns of relationships between parents and progeny for each phenotypic trait, including (i) similar to one of the parents, (ii) intermediate between the parents, and (iii) outside the parental phenotypic range. We found that as genetic distance increases between parental strains, progeny showed increased fluconazole resistance and growth at 37 °C but decreased melanin production under various oxidative and nitrosative stresses. Our findings demonstrate that, depending on the traits, both evolutionarily more similar strains and more divergent strains may be better parents to generate progeny with hybrid vigor. Together, the results indicate the enormous potential of Cryptococcus hybrids in their evolution and adaptation to diverse conditions.

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