Faculty Opinions recommendation of Transcriptional response of Candida albicans to hypoxia: linkage of oxygen sensing and Efg1p-regulatory networks.

Abstract The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal homeostasis, we sought to address how the availability of copper in particular impacts the response of the opportunistic fungal pathogen Candida albicans to treatment with the antifungal drug fluconazole. The present study reports whole transcriptome analysis via time-course RNA-seq of C. albicans cells exposed to fluconazole with and without 10 µM supplemental CuSO4 added to the growth medium. The results show widespread impacts of small changes in Cu availability on the transcriptional response of C. albicans to fluconazole. Of the 2359 genes that were differentially expressed under conditions of cotreatment, 50% were found to be driven uniquely by exposure to both Cu and fluconazole. The breadth of metabolic processes that were affected by cotreatment illuminates a fundamental intersectionality between Cu metabolism and fungal response to drug stress. More generally, these results show that seemingly minor fluctuations in Cu availability are sufficient to shift cells’ transcriptional response to drug stress. Ultimately, the findings may inform the development of new strategies that capitalize on drug-induced vulnerabilities in metal homeostasis pathways.

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The Early Transcriptional Response of Human Granulocytes to Infection with Candida albicans Is Not Essential for Killing but Reflects Cellular Communications

Infection and Immunity ◽

10.1128/iai.01651-06 ◽

2006 ◽

Vol 75 (3) ◽

pp. 1493-1501 ◽

Cited By ~ 28

Author(s):

Chantal Fradin ◽

Abigail L. Mavor ◽

Günther Weindl ◽

Martin Schaller ◽

Karin Hanke ◽

...

Keyword(s):

Candida Albicans ◽

Mononuclear Cells ◽

De Novo ◽

Transcriptional Response ◽

Mononuclear Leukocytes ◽

General Notion ◽

Genes Encoding ◽

Global Transcriptional Profile ◽

Life Threatening ◽

Systemic Infections

ABSTRACT Candida albicans is a polymorphic opportunistic fungus that can cause life-threatening systemic infections following hematogenous dissemination in patients susceptible to nosocomial infection. Neutrophils form part of the innate immune response, which is the first line of defense against microbes and is particularly important in C. albicans infections. To compare the transcriptional response of leukocytes exposed to C. albicans, we investigated the expression of key cytokine genes in polymorphonuclear and mononuclear leukocytes after incubation with C. albicans for 1 h. Isolated mononuclear cells expressed high levels of genes encoding proinflammatory signaling molecules, whereas neutrophils exhibited much lower levels, similar to those observed in whole blood. The global transcriptional profile of neutrophils was examined by using an immunology-biased human microarray to determine whether different morphological forms or the viability of C. albicans altered the transcriptome. Hyphal cells appeared to have the broadest effect, although the most strongly induced genes were regulated independently of morphology or viability. These genes were involved in proinflammatory cell-cell signaling, cell signal transduction, and cell growth. Generally, genes encoding known components of neutrophil granules showed no upregulation at this time point; however, lactoferrin, a well-known candidacidal peptide, was secreted by neutrophils. Addition to inhibitors of RNA or protein de novo synthesis did not influence the killing activity within 30 min. These results support the general notion that neutrophils do not require gene transcription to mount an immediate and direct attack against microbes. However, neutrophils exposed to C. albicans express genes involved in communication with other immune cells.

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Nonlinear feedback drives homeostatic plasticity in H2O2 stress response

eLife ◽

10.7554/elife.23971 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 29

Author(s):

Youlian Goulev ◽

Sandrine Morlot ◽

Audrey Matifas ◽

Bo Huang ◽

Mikael Molin ◽

...

Keyword(s):

Live Cell Imaging ◽

Regulatory Networks ◽

Transcriptional Response ◽

Genetic Regulatory Networks ◽

Homeostatic Plasticity ◽

Mild Stress ◽

Molecular Architecture ◽

Nonlinear Feedback ◽

Hormetic Effect ◽

Stress Patterns

Homeostatic systems that rely on genetic regulatory networks are intrinsically limited by the transcriptional response time, which may restrict a cell’s ability to adapt to unanticipated environmental challenges. To bypass this limitation, cells have evolved mechanisms whereby exposure to mild stress increases their resistance to subsequent threats. However, the mechanisms responsible for such adaptive homeostasis remain largely unknown. Here, we used live-cell imaging and microfluidics to investigate the adaptive response of budding yeast to temporally controlled H2O2 stress patterns. We demonstrate that acquisition of tolerance is a systems-level property resulting from nonlinearity of H2O2 scavenging by peroxiredoxins and our study reveals that this regulatory scheme induces a striking hormetic effect of extracellular H2O2 stress on replicative longevity. Our study thus provides a novel quantitative framework bridging the molecular architecture of a cellular homeostatic system to the emergence of nonintuitive adaptive properties.

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Transcriptional response to fluconazole and amphotericin B in Candida albicans biofilms

Research in Microbiology ◽

10.1016/j.resmic.2010.02.004 ◽

2010 ◽

Vol 161 (4) ◽

pp. 284-292 ◽

Cited By ~ 31

Author(s):

Heleen Nailis ◽

Davy Vandenbosch ◽

Dieter Deforce ◽

Hans J. Nelis ◽

Tom Coenye

Keyword(s):

Candida Albicans ◽

Amphotericin B ◽

Transcriptional Response ◽

Candida Albicans Biofilms

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Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood

Molecular Microbiology ◽

10.1111/j.1365-2958.2005.04557.x ◽

2005 ◽

Vol 56 (2) ◽

pp. 397-415 ◽

Cited By ~ 316

Author(s):

Chantal Fradin ◽

Piet De Groot ◽

Donna MacCallum ◽

Martin Schaller ◽

Frans Klis ◽

...

Keyword(s):

Candida Albicans ◽

Human Blood ◽

Transcriptional Response

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Prediction of Whole-Cell Transcriptional Response with Machine Learning

Bioinformatics ◽

10.1093/bioinformatics/btab676 ◽

2021 ◽

Author(s):

Mohammed Eslami ◽

Amin Espah-Borujeni ◽

Hamed Eramian ◽

Mark Weston ◽

George Zheng ◽

...

Keyword(s):

Machine Learning ◽

Differential Expression ◽

Regulatory Networks ◽

High Throughput Sequencing ◽

Differential Expression Analysis ◽

Transcriptional Response ◽

Predictive Performance ◽

Supplementary Information ◽

Whole Cell ◽

Using Data

Abstract Motivation Applications in synthetic and systems biology can benefit from measuring whole-cell response to biochemical perturbations. Execution of experiments to cover all possible combinations of perturbations is infeasible. In this paper, we present the host response model (HRM), a machine learning approach that maps response of single perturbations to transcriptional response of the combination of perturbations. Results The HRM combines high-throughput sequencing with machine learning to infer links between experimental context, prior knowledge of cell regulatory networks, and RNASeq data to predict a gene’s dysregulation. We find that the HRM can predict the directionality of dysregulation to a combination of inducers with an accuracy of > 90% using data from single inducers. We further find that the use of prior, known cell regulatory networks doubles the predictive performance of the HRM (an R2 from 0.3 to 0.65). The model was validated in two organisms, E. coli and B. subtilis, using new experiments conducted post training. Finally, while the HRM is trained on gene expression data, the direct prediction of differential expression makes it possible to also conduct enrichment analyses using its predictions. We show that the HRM can accurately classify >95% of the pathway regulations. The HRM reduces the number of RNASeq experiments needed as responses can be tested in-silico to focus experiments. Availability The HRM software and tutorial are available at https://github.com/sd2e/CDM and the configurable differential expression analysis tools and tutorials are available at https://github.com/SD2E/omics_tools. Supplementary information Supplementary data are available at Bioinformatics online.

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Regulatory networks affected by iron availability in Candida albicans

Molecular Microbiology ◽

10.1111/j.1365-2958.2004.04214.x ◽

2004 ◽

Vol 53 (5) ◽

pp. 1451-1469 ◽

Cited By ~ 184

Author(s):

Chung-Yu Lan ◽

Gabriel Rodarte ◽

Luis A. Murillo ◽

Ted Jones ◽

Ronald W. Davis ◽

...

Keyword(s):

Candida Albicans ◽

Regulatory Networks ◽

Iron Availability

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N-acetylglucosamine Signaling: Transcriptional Dynamics of a Novel Sugar Sensing Cascade in a Model Pathogenic Yeast, Candida albicans

Journal of Fungi ◽

10.3390/jof7010065 ◽

2021 ◽

Vol 7 (1) ◽

pp. 65

Author(s):

Kongara Hanumantha Rao ◽

Soumita Paul ◽

Swagata Ghosh

Keyword(s):

Candida Albicans ◽

Transcriptional Response ◽

Amino Sugar ◽

Therapeutic Interventions ◽

Gene Promoters ◽

Catabolic Gene ◽

Pathogenic Yeast ◽

Cellular Processes ◽

Transcriptional Dynamics ◽

Recent Developments

The amino sugar, N-acetylglucosamine (GlcNAc), has emerged as an attractive messenger of signaling in the pathogenic yeast Candida albicans, given its multifaceted role in cellular processes, including GlcNAc scavenging, import and metabolism, morphogenesis (yeast to hyphae and white to opaque switch), virulence, GlcNAc induced cell death (GICD), etc. During signaling, the exogenous GlcNAc appears to adopt a simple mechanism of gene regulation by directly activating Ngs1, a novel GlcNAc sensor and transducer, at the chromatin level, to activate transcriptional response through the promoter acetylation. Ngs1 acts as a master regulator in GlcNAc signaling by regulating GlcNAc catabolic gene expression and filamentation. Ndt80-family transcriptional factor Rep1 appears to be involved in the recruitment of Ngs1 to GlcNAc catabolic gene promoters. For promoting filamentation, GlcNAc adopts a little modified strategy by utilizing a recently evolved transcriptional loop. Here, Biofilm regulator Brg1 takes up the key role, getting up-regulated by Ngs1, and simultaneously induces Hyphal Specific Genes (HSGs) expression by down-regulating NRG1 expression. GlcNAc kinase Hxk1 appears to play a prominent role in signaling. Recent developments in GlcNAc signaling have made C. albicans a model system to understand its role in other eukaryotes as well. The knowledge thus gained would assist in designing therapeutic interventions for the control of candidiasis and other fungal diseases.

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Identification of a Salmonella ancillary copper detoxification mechanism by a comparative analysis of the genome-wide transcriptional response to copper and zinc excess

Microbiology ◽

10.1099/mic.0.080473-0 ◽

2014 ◽

Vol 160 (8) ◽

pp. 1659-1669 ◽

Cited By ~ 16

Author(s):

Lucas B. Pontel ◽

Nadia L. Scampoli ◽

Steffen Porwollik ◽

Susana K. Checa ◽

Michael McClelland ◽

...

Keyword(s):

Metal Ions ◽

Stress Responses ◽

Regulatory Networks ◽

Iron Homeostasis ◽

Transcriptional Response ◽

Zinc Excess ◽

Copper And Zinc ◽

Genome Wide ◽

Copper Excess ◽

Upregulated Genes

Copper and zinc are essential metal ions, but toxic in excess. Bacteria have evolved different strategies to control their intracellular concentrations, ensuring proper supply while avoiding toxicity, including the induction of metal-specific as well as non-specific mechanisms. We compared the transcriptional profiles of Salmonella Typhimurium after exposure to either copper or zinc ions in both rich and minimal media. Besides metal-specific regulatory networks many global stress-response pathways react to an excess of either of these metal ions. Copper excess affects both zinc and iron homeostasis by inducing transcription of these metal-specific regulons. In addition to the control of zinc-specific regulons, zinc excess affects the Cpx regulon and the σE envelope-stress responses. Finally, novel metal-specific upregulated genes were detected including a new copper-detoxification pathway that involves the siderophore enterobactin and the outer-membrane protein TolC. This work sheds light onto the transcriptional landscape of Salmonella after copper or zinc overload, and discloses a new mechanism of copper detoxification.

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