Expression Patterns in Reductive Iron Assimilation and Functional Consequences during Phagocytosis of Lichtheimia corymbifera, an Emerging Cause of Mucormycosis

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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Expression profiling of purified male germ cells: stage-specific expression patterns related to meiosis and postmeiotic development

Physiological Genomics ◽

10.1152/physiolgenomics.00215.2004 ◽

2006 ◽

Vol 24 (2) ◽

pp. 75-85 ◽

Cited By ~ 36

Author(s):

Alan L. Y. Pang ◽

Warren Johnson ◽

Neelakanta Ravindranath ◽

Martin Dym ◽

Owen M. Rennert ◽

...

Keyword(s):

Gene Expression ◽

Germ Cells ◽

Expression Profiling ◽

Intracellular Transport ◽

Expression Patterns ◽

Male Gamete ◽

Specific Expression ◽

Differential Expression Pattern ◽

Pachytene Spermatocytes ◽

Cycle Regulation

Gene expression profiling was performed using the National Institute on Aging 15,000-cDNA microarray to reveal the differential expression pattern of 160 genes between meiotic pachytene spermatocytes and postmeiotic round spermatids of the mouse. Our results indicate that more genes are expressed in spermatids than in spermatocytes. Genes participating in cell cycle regulation and chromatin structure and dynamics are preferentially expressed in spermatocytes, while genes for protein turnover, signal transduction, energy metabolism, and intracellular transport are prevalent in spermatids. This suggests that a switch of functional requirement occurs when meiotic germ cells differentiate into haploid spermatids. Concordant expression patterns were obtained when quantitative real-time polymerase chain reaction was performed to verify the microarray data. Interestingly, the majority of the differentially expressed genes were underrepresented in mitotic type A spermatogonia, and they were preferentially expressed in the testis. Our results suggest that an even higher proportion of the mouse genome is devoted to male gamete development from meiosis than was previously estimated. We also provide evidence that underscores the advantage of using purified germ cells over whole testes in profiling spermatogenic gene expression to identify transcripts that demonstrate stage-specific expression patterns.

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Clinical phenotype and gene expression profile in Crohn's disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00321.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. G298-G304 ◽

Cited By ~ 13

Author(s):

Claudio Csillag ◽

Ole Haagen Nielsen ◽

Rehannah Borup ◽

Finn Cilius Nielsen ◽

Jørgen Olsen

Keyword(s):

Gene Expression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intracellular Transport ◽

Clinical Phenotype ◽

Expression Profiles ◽

Expression Patterns ◽

Principal Component ◽

Gene Profiling ◽

Gene Expression Patterns

The clinical course varies significantly among patients with Crohn's disease (CD). This study investigated whether gene expression profiles generated by DNA microarray technology might predict disease progression. Biopsies from the descending colon were obtained colonoscopically from 40 CD patients. Gene profiling analyses were performed using a Human Genome U133 Plus 2.0 GeneChip Array, and summarization into a single expression measure for each probe set was performed using the robust multiple array procedure. Principal component analysis demonstrated that three components explain two-thirds of the total variation. The most important parameters for the determination of the colonic gene expression patterns were the presence of disease (CD) and presence of inflammation. Superimposition of clinical phenotype data revealed a grouping of the samples from patients with stenosis toward negative values on the axis of the second principal component. The functional annotation analysis suggested that the expression of genes involved in intracellular transport and cytoskeletal organization might influence the development of stenosis. In conclusion, even though most variation in the colonic gene expression patterns is due to presence or absence of CD and inflammation status, the development of stenosis is a parameter that affects colonic gene expression to some extent.

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Phase-specific gene expression underlying morphological adaptations of the dimorphic human pathogenic fungus, Coccidioides posadasii

Fungal Genetics and Biology ◽

10.1016/j.fgb.2006.02.003 ◽

2006 ◽

Vol 43 (8) ◽

pp. 545-559 ◽

Cited By ~ 19

Author(s):

H. Johannesson ◽

T. Kasuga ◽

R.A. Schaller ◽

B. Good ◽

M.J. Gardner ◽

...

Keyword(s):

Gene Expression ◽

Pathogenic Fungus ◽

Specific Gene ◽

Coccidioides Posadasii ◽

Specific Gene Expression ◽

Morphological Adaptations ◽

Human Pathogenic Fungus

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

Molecular Genetics and Genomics ◽

10.1007/s00438-016-1184-1 ◽

2016 ◽

Vol 291 (3) ◽

pp. 1347-1362 ◽

Cited By ~ 5

Author(s):

Daniela Leite Jabes ◽

Ana Claudia de Freitas Oliveira ◽

Valquíria Campos Alencar ◽

Fabiano Bezerra Menegidio ◽

Débora Liliane Souza Reno ◽

...

Keyword(s):

Gene Expression ◽

Cell Wall ◽

Signaling Pathway ◽

Paracoccidioides Brasiliensis ◽

Pathogenic Fungus ◽

Expression Control ◽

Gene Expression Control ◽

Human Pathogenic Fungus

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New Putative Long Non-Coding RNAs (lncRNA) Revealed by Pan-Transcriptome of the Emerging Human Pathogenic Fungus Talaromyces Marneffei

10.21203/rs.3.rs-1050608/v1 ◽

2021 ◽

Author(s):

David Aciole Barbosa ◽

Alexandre Santos Simeone ◽

Ana Carolina Humberto ◽

Yara Natercia Lima Faustino de Maria ◽

Regina Costa de Oliveira ◽

...

Keyword(s):

Gene Expression ◽

Transcriptome Assembly ◽

Pathogenic Fungus ◽

The Novel ◽

Talaromyces Marneffei ◽

Expression Control ◽

Gene Expression Control ◽

Human Pathogenic Fungus ◽

Non Coding Rnas

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.

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Yeast cell cycle protein CDC48p shows full-length homology to the mammalian protein VCP and is a member of a protein family involved in secretion, peroxisome formation, and gene expression.

The Journal of Cell Biology ◽

10.1083/jcb.114.3.443 ◽

1991 ◽

Vol 114 (3) ◽

pp. 443-453 ◽

Cited By ~ 207

Author(s):

K U Fröhlich ◽

H W Fries ◽

M Rüdiger ◽

R Erdmann ◽

D Botstein ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Fusion Protein ◽

Intracellular Transport ◽

Consensus Sequence ◽

Cell Cycle Gene ◽

Cell Cycle Protein ◽

A Cell ◽

Yeast Mutants ◽

Mammalian Protein

Yeast mutants of cell cycle gene cdc48-1 arrest as large budded cells with microtubules spreading aberrantly throughout the cytoplasm from a single spindle plaque. The gene was cloned and disruption proved it to be essential. The CDC48 sequence encodes a protein of 92 kD that has an internal duplication of 200 amino acids and includes a nucleotide binding consensus sequence. Vertebrate VCP has a 70% identity over the entire length of the protein. Yeast Sec18p and mammalian N-ethylmaleimide-sensitive fusion protein, which are involved in intracellular transport, yeast Pas1p, which is essential for peroxisome assembly, and mammalian TBP-1, which influences HIV gene expression, are 40% identical in the duplicated region. Antibodies against CDC48 recognize a yeast protein of apparently 115 kD and a mammalian protein of 100 kD. Both proteins are bound loosely to components of the microsomal fraction as described for Sec18p and N-ethylmaleimide-sensitive fusion protein. This similarity suggests that CDC48p participates in a cell cycle function related to that of N-ethylmaleimide-sensitive fusion protein/Sec18p in Golgi transport.

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Functional analysis of the phospholipase C gene CaPLC1 and two unusual phospholipase C genes, CaPLC2 and CaPLC3, of Candida albicans

Microbiology ◽

10.1099/mic.0.28353-0 ◽

2005 ◽

Vol 151 (10) ◽

pp. 3381-3394 ◽

Cited By ~ 27

Author(s):

Donika Kunze ◽

Inga Melzer ◽

Désirée Bennett ◽

Dominique Sanglard ◽

Donna MacCallum ◽

...

Keyword(s):

Candida Albicans ◽

Phospholipase C ◽

Essential Gene ◽

Pathogenic Fungus ◽

Systemic Infection ◽

Cellular Processes ◽

Solid Media ◽

Transcriptional Pattern ◽

Human Pathogenic Fungus ◽

Hyphal Formation

Phospholipases C are known to be important regulators of cellular processes but may also act as virulence factors of pathogenic microbes. At least three genes in the genome of the human-pathogenic fungus Candida albicans encode phospholipases with conserved phospholipase C (Plc) motifs. None of the deduced protein sequences contain N-terminal signal peptides, suggesting that these phospholipases are not secreted. In contrast to its orthologue in Sacharomyces cerevisiae, CaPLC1 seems to be an essential gene. However, a conditional mutant with reduced transcript levels of CaPLC1 had phenotypes similar to Plc1p-deficient mutants in S. cerevisiae, including reduced growth on media causing increased osmotic stress, on media with a non-glucose carbon source, or at elevated or lower temperatures, suggesting that CaPlc1p, like the Plc1p counterpart in S. cerevisiae, may be involved in multiple cellular processes. Furthermore, phenotypic screening of the heterozygous ΔCaplc1/CaPLC1 mutant showed additional defects in hyphal formation. The loss of CaPLC1 cannot be compensated by two additional PLC genes of C. albicans (CaPLC2 and CaPLC3) encoding two almost identical phospholipases C with no counterpart in S. cerevisiae but containing structural elements found in bacterial phospholipases C. Although the promoter sequences of CaPLC2 and CaPLC3 differed dramatically, the transcriptional pattern of both genes was similar. In contrast to CaPLC1, CaPLC2 and CaPLC3 are not essential. Although Caplc2/3 mutants had reduced abilities to produce hyphae on solid media, these mutants were as virulent as the wild-type in a model of systemic infection. These data suggest that C. albicans contains two different classes of phospholipases C which are involved in cellular processes but which have no specific functions in pathogenicity.

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Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart

Physiological Genomics ◽

10.1152/physiolgenomics.00229.2003 ◽

2005 ◽

Vol 20 (3) ◽

pp. 211-223 ◽

Cited By ~ 34

Author(s):

Dumitru A. Iacobas ◽

Sanda Iacobas ◽

W. E. I. Li ◽

Georg Zoidl ◽

Rolf Dermietzel ◽

...

Keyword(s):

Gene Expression ◽

Intracellular Transport ◽

Expression Patterns ◽

Sympathetic Innervation ◽

Adrenergic Nerve ◽

Null Mouse ◽

Mouse Heart ◽

Mouse Tissues ◽

Junction Protein ◽

Glial Function

We have used mouse 27k cDNA arrays to compare gene expression patterns in four sets of three hearts each of neonatal wild types and four sets of three hearts each of littermates lacking the major cardiac gap junction protein, connexin43 (Cx43). Each individual set of hearts was hybridized against aliquots of an RNA standard prepared from selected mouse tissues, allowing calculation of variability and coordination of gene expression among the samples from both genotypes. Overall variance of gene expression was found to be markedly higher in wild-type hearts than in those from Cx43 null littermates. Expression levels of 586 of 5,613 adequately quantifiable distinct genes with known protein products were statistically altered in the Cx43 null hearts, 38 upregulated and 548 downregulated compared with wild types. Downregulation was confirmed for seven tested genes by quantitative RT-PCR. Functions of proteins encoded by the altered genes encompassed all functional categories, with largest percent changes in genes involved in intracellular transport and transcription factors. Among the downregulated genes in the Cx43 null hearts were those related to neuronal and glial function, suggesting that cardiac innervation might be compromised as a consequence of Cx43 deletion. This was supported by immunodetection of sympathetic innervation, using antibodies to the synaptic vesicle protein synaptophysin and to the adrenergic nerve terminal marker tyrosine hydroxylase. These findings reinforce the proposal that the cardiac abnormality in Cx43 null animals may be contributed by altered innervation and indicate that Cx43 deletion has consequences in addition to reduced intercellular communication.

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