scholarly journals On and Off: Epigenetic Regulation of C. albicans Morphological Switches

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1463
Author(s):  
Elise Iracane ◽  
Samuel Vega-Estévez ◽  
Alessia Buscaino
Keyword(s):  
Epigenetic Regulation ◽  
Biofilm Formation ◽  
Transcriptional Regulatory Network ◽  
Opportunistic Pathogen ◽  
Human Fungal Pathogen ◽  
Transcriptional Regulatory ◽  
Life Threatening ◽  
Morphological Transitions ◽  
Non Coding Rnas ◽  
Epigenetic Modulation

The human fungal pathogen Candida albicans is a dimorphic opportunistic pathogen that colonises most of the human population without creating any harm. However, this fungus can also cause life-threatening infections in immunocompromised individuals. The ability to successfully colonise different host niches is critical for establishing infections and pathogenesis. C. albicans can live and divide in various morphological forms critical for its survival in the host. Indeed, C. albicans can grow as both yeast and hyphae and can form biofilms containing hyphae. The transcriptional regulatory network governing the switching between these different forms is complex but well understood. In contrast, non-DNA based epigenetic modulation is emerging as a crucial but still poorly studied regulatory mechanism of morphological transition. This review explores our current understanding of chromatin-mediated epigenetic regulation of the yeast to hyphae switch and biofilm formation. We highlight how modification of chromatin structure and non-coding RNAs contribute to these morphological transitions.

scholarly journals Interactions between Candida albicans and Enterococcus faecalis in an Organotypic Oral Epithelial Model

2020 ◽  
Vol 8 (11) ◽  
pp. 1771
Author(s):  
Akshaya Lakshmi Krishnamoorthy ◽  
Alex A. Lemus ◽  
Adline Princy Solomon ◽  
Alex M. Valm ◽  
Prasanna Neelakantan
Keyword(s):  
Candida Albicans ◽  
Enterococcus Faecalis ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Surface Erosion ◽  
Host Immune System ◽  
Microbial Invasion ◽  
Mucosal Surfaces ◽  
Life Threatening ◽  
Hyphal Formation

Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause oral and disseminated infections. Similar to C. albicans, Enterococcus faecalis is a major opportunistic pathogen, which is of critical concern in immunocompromised patients. There is increasing evidence that E. faecalis co-exists with C. albicans in the human body in disease samples. While the interactive profiles between these two organisms have been studied on abiotic substrates and mouse models, studies on their interactions on human oral mucosal surfaces are non-existent. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and P52S) on an organotypic oral mucosal model. Our results demonstrated that the dual species biofilms resulted in profound surface erosion and significantly increased microbial invasion into mucosal compartments, compared to either species alone. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. By contrast, E. faecalis genes involved in quorum sensing, biofilm formation, virulence, and mammalian cell invasion were downregulated. This study highlights the synergistic cross-kingdom interactions between E. faecalis and C. albicans in mucosal tissue invasion.

scholarly journals Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin Rychel ◽  
Anand V. Sastry ◽  
Bernhard O. Palsson
Keyword(s):  
Machine Learning ◽  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Transcriptional Regulatory Network ◽  
Population Level ◽  
Cellular Functions ◽  
Fundamental Interest ◽  
Gene Sets ◽  
Transcriptional Regulatory ◽  
Dependent Activity

AbstractThe transcriptional regulatory network (TRN) of Bacillus subtilis coordinates cellular functions of fundamental interest, including metabolism, biofilm formation, and sporulation. Here, we use unsupervised machine learning to modularize the transcriptome and quantitatively describe regulatory activity under diverse conditions, creating an unbiased summary of gene expression. We obtain 83 independently modulated gene sets that explain most of the variance in expression and demonstrate that 76% of them represent the effects of known regulators. The TRN structure and its condition-dependent activity uncover putative or recently discovered roles for at least five regulons, such as a relationship between histidine utilization and quorum sensing. The TRN also facilitates quantification of population-level sporulation states. As this TRN covers the majority of the transcriptome and concisely characterizes the global expression state, it could inform research on nearly every aspect of transcriptional regulation in B. subtilis.

scholarly journals Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of the Pathogenic Yeast Candida albicans

Antibiotics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Untreated Control ◽  
Morphological Transition ◽  
Pathogenic Yeast ◽  
Yeast Form ◽  
Human Fungal Pathogen ◽  
Morphological Transitions ◽  
Simple Carbohydrate

The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.

scholarly journals Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of Candida albicans

2019 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Untreated Control ◽  
Morphological Transition ◽  
Yeast Form ◽  
Polystyrene Surface ◽  
Human Fungal Pathogen ◽  
Morphological Transitions ◽  
Simple Carbohydrate

Abstract The opportunistic human fungal pathogen Candida albicans rely on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-L-fucopyranoside and benzyl β-D-xylopyranoside, inhibit the morphological switching and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-L-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-D-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.

scholarly journals Candida glabrata: A Lot More Than Meets the Eye

2019 ◽  
Vol 7 (2) ◽  
pp. 39 ◽  
Author(s):  
Kundan Kumar ◽  
Fizza Askari ◽  
Mahima Sahu ◽  
Rupinder Kaur
Keyword(s):  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Candida Glabrata ◽  
External Environment ◽  
Bloodstream Infections ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pathogenic Yeast ◽  
Human Fungal Pathogen ◽  
Life Threatening ◽  
Inflammatory Immune Response

Candida glabrata is an opportunistic human fungal pathogen that causes superficial mucosal and life-threatening bloodstream infections in individuals with a compromised immune system. Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans. C. glabrata is a haploid budding yeast that predominantly reproduces clonally. In this review, we summarize interactions of C. glabrata with the host immune, epithelial and endothelial cells, and the ingenious strategies it deploys to acquire iron and phosphate from the external environment. We outline various attributes including cell surface-associated adhesins and aspartyl proteases, biofilm formation and stress response mechanisms, that contribute to the virulence of C. glabrata. We further discuss how, C. glabrata, despite lacking morphological switching and secreted proteolytic activity, is able to disarm macrophage, dampen the host inflammatory immune response and replicate intracellularly.

scholarly journals Recent advances on Candida albicans biology and virulence

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2582 ◽  
Author(s):  
Adnane Sellam ◽  
Malcolm Whiteway
Keyword(s):  
Candida Albicans ◽  
Drug Targets ◽  
Opportunistic Pathogen ◽  
Antifungal Drugs ◽  
Human Fungal Pathogen ◽  
Recent Developments ◽  
Immunosuppressed Patients ◽  
Technical Advances ◽  
Life Threatening ◽  
Human Flora

Candida albicans is an important human fungal pathogen, in terms of both its clinical significance and its use as an experimental model for scientific investigation. Although this opportunistic pathogen is a natural component of the human flora, it can cause life-threatening infections in immunosuppressed patients. There are currently a limited number of antifungal molecules and drug targets, and increasing resistance to the front-line therapeutics, demonstrating a clear need for new antifungal drugs. Understanding the biology of this pathogen is an important prerequisite for identifying new drug targets for antifungal therapeutics. In this review, we highlight some recent developments that help us to understand how virulence traits are regulated at the molecular level, in addition to technical advances that improve the ability of genome editing in C. albicans.

scholarly journals Multiplex CRISPRi-Cas9 silencing of planktonic and stage-specific biofilm genes in Enterococcus faecalis

2020 ◽  
Author(s):  
Irina Afonina ◽  
June Ong ◽  
Jerome Chua ◽  
Timothy Lu ◽  
Kimberly A. Kline
Keyword(s):  
Enterococcus Faecalis ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Expression System ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
Essential Genes ◽  
Dual Vector ◽  
Wide Range ◽  
Life Threatening

ABSTRACTEnterococcus faecalis is an opportunistic pathogen, which can cause multidrug-resistant life-threatening infections. Gaining a complete understanding of enterococcal pathogenesis is a crucial step in identifying a strategy to effectively treat enterococcal infections. However, bacterial pathogenesis is a complex process often involving a combination of genes and multi-level regulation. Compared to established knockout methodologies, CRISPRi approaches enable rapid and efficient silencing of genes to interrogate gene products and pathways involved in pathogenesis. As opposed to traditional gene inactivation approaches, CRISPRi can also be quickly repurposed for multiplexing or used to study essential genes. Here we have developed a novel dual-vector nisin-inducible CRISPRi system in E. faecalis that can efficiently silence via both non-template and template strand targeting. Since nisin-controlled gene expression system is functional in various Gram-positive bacteria, the developed CRISPRi tool can be extended to other genera. This system can be applied to study essential genes, genes involved in antimicrobial resistance, and genes involved in biofilm formation and persistence. The system is robust, and can be scaled up for high-throughput screens or combinatorial targeting. This tool substantially enhances our ability to study enterococcal biology and pathogenesis, host-bacteria interactions, and inter-species communication.IMPORTANCEEnterococcus faecalis causes multidrug resistant life-threatening infections, and is often co-isolated with other pathogenic bacteria from polymicrobial biofilm-associated infections. Genetic tools to dissect complex interactions in mixed microbial communities are largely limited to transposon mutagenesis and traditional time- and labour-intensive allelic exchange methods. Built upon streptococcal dCas9, we developed an easily-modifiable, inducible CRISPRi system for E. faecalis that can efficiently silence single and multiple genes. This system can silence genes involved in biofilm formation, antibiotic resistance, and can be used to interrogate gene essentiality. Uniquely, this tool is optimized to study genes important for biofilm initiation, maturation, and maintenance, and can be used to perturb pre-formed biofilms. This system will be valuable to rapidly and efficiently investigate a wide range of aspects of complex enterococcal biology.

scholarly journals Simple Carbohydrate Derivatives Diminish the Formation of Biofilm of Candida albicans

2019 ◽  
Author(s):  
Olena P. Ishchuk ◽  
Olov Sterner ◽  
Ulf Ellervik ◽  
Sophie Manner
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Untreated Control ◽  
Morphological Transition ◽  
Yeast Form ◽  
Polystyrene Surface ◽  
Human Fungal Pathogen ◽  
Morphological Transitions ◽  
Simple Carbohydrate

Abstract The opportunistic human fungal pathogen Candida albicans rely on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-L-fucopyranoside and benzyl β-D-xylopyranoside, inhibit the morphological switching and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-L-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-D-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.

scholarly journals Antibacterial and Antivirulence Activity of Glucocorticoid PYED-1 against Stenotrophomonas maltophilia

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 105 ◽  
Author(s):  
Anna Esposito ◽  
Adriana Vollaro ◽  
Eliana Pia Esposito ◽  
Daniele D’Alonzo ◽  
Annalisa Guaragna ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Stenotrophomonas Maltophilia ◽  
Opportunistic Pathogen ◽  
Pulmonary Infections ◽  
Negative Bacterium ◽  
Standard Strain ◽  
Chain Reaction ◽  
Qpcr Analysis ◽  
Life Threatening ◽  
Polymerase Chain

Stenotrophomonas maltophilia, an environmental Gram-negative bacterium, is an emerging nosocomial opportunistic pathogen that causes life-threatening infections in immunocompromised patients and chronic pulmonary infections in cystic fibrosis patients. Due to increasing resistance to multiple classes of antibiotics, S. maltophilia infections are difficult to treat successfully. This makes the search for new antimicrobial strategies mandatory. In this study, the antibacterial activity of the heterocyclic corticosteroid deflazacort and several of its synthetic precursors was tested against S. maltophilia. All compounds were not active against standard strain S. maltophilia K279a. The compound PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) showed a weak effect against some S. maltophilia clinical isolates, but exhibited a synergistic effect with aminoglycosides. PYED-1 at sub-inhibitory concentrations decreased S. maltophilia biofilm formation. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis demonstrated that the expression of biofilm- and virulence- associated genes (StmPr1, StmPr3, sphB, smeZ, bfmA, fsnR) was significantly suppressed after PYED-1 treatment. Interestingly, PYED-1 also repressed the expression of the genes aph (3′)-IIc, aac (6′)-Iz, and smeZ, involved in the resistance to aminoglycosides.

scholarly journals Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 208 ◽  
Author(s):  
Fazlurrahman Khan ◽  
Panchanathan Manivasagan ◽  
Jang-Won Lee ◽  
Dung Pham ◽  
Junghwan Oh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Growth ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Brown Seaweed ◽  
Opportunistic Pathogen ◽  
Biofilm Inhibition ◽  
Transmission Electron ◽  
Inhibition Concentration ◽  
Life Threatening

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

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