High Frequency Variation of Colony Morphology and Chromosome Reorganization in the Pathogenic Yeast Candida albicans

Candida albicansis a pathogenic yeast that causes mucosal and systematic infections with high mortality. The absence of facile molecular genetics has been a major impediment to analysis of pathogenesis. The lack of meiosis coupled with the absence of plasmids makes genetic engineering cumbersome, especially for essential functions and gene families. We describe aC. albicansCRISPR system that overcomes many of the obstacles to genetic engineering in this organism. The high frequency with which CRISPR-induced mutations can be directed to target genes enables easy isolation of homozygous gene knockouts, even without selection. Moreover, the system permits the creation of strains with mutations in multiple genes, gene families, and genes that encode essential functions. This CRISPR system is also effective in a fresh clinical isolate of undetermined ploidy. Our method transforms the ability to manipulate the genome ofCandidaand provides a new window into the biology of this pathogen.

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High-frequency switching of colony morphology in Candida albicans

Science ◽

10.1126/science.3901258 ◽

1985 ◽

Vol 230 (4726) ◽

pp. 666-669 ◽

Cited By ~ 242

Author(s):

B Slutsky ◽

J Buffo ◽

D. Soll

Keyword(s):

Candida Albicans ◽

High Frequency ◽

Colony Morphology

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Faculty Opinions recommendation of Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1084978.537944 ◽

2007 ◽

Author(s):

Juergen Wendland

Keyword(s):

Candida Albicans ◽

Pathogenic Yeast ◽

Experimental Approaches

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Ultrastructural Changes of Candida albicans Species Induced by the Presence of Sodium Diclofenac

Revista de Chimie ◽

10.37358/rc.17.11.5929 ◽

2017 ◽

Vol 68 (11) ◽

pp. 2566-2569 ◽

Cited By ~ 1

Author(s):

Elena Rusu ◽

Ionela Sarbu ◽

Magdalena Mitache ◽

Horatiu Moldovan ◽

Carmen Ioana Biris ◽

...

Keyword(s):

Candida Albicans ◽

High Frequency ◽

Fungal Infections ◽

Diagnostic Methods ◽

Ultrastructural Changes ◽

Frequency Of Occurrence ◽

Medical Treatments ◽

Sodium Diclofenac ◽

Cell Wall Disruption ◽

Candidiasis Treatment

The high frequency of occurrence of candidiasis as well as high mortality of patients with immunosuppression cause a tendency toward better understanding of Candida albicans species virulence factors and developing sensitive and specific diagnostic methods, and appropriate strategies of candidiasis treatment. In recent decades the incidence of fungal infections has alarming increases because of advanced medical treatments. In this study was analyzed possible ultrastructural changes of the species C. albicans cells following treatment with sodium diclofenac at various concentrations. Following treatment of C. albicans cells with sodium diclofenac 1 mM and 2 mM changes in the plasmalemma can be noticed, changes in the density of cell wall, disruption and necrotic appearance of the cytoplasm.

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Bioactive Coatings with Ag-Camphorimine Complexes to Prevent Surface Colonization by the Pathogenic Yeast Candida albicans

Antibiotics ◽

10.3390/antibiotics10060638 ◽

2021 ◽

Vol 10 (6) ◽

pp. 638

Author(s):

M. Joana F. Pinheiro ◽

Joana P. Costa ◽

Fernanda Marques ◽

Nuno P. Mira ◽

M. Fernanda N. N. Carvalho ◽

...

Keyword(s):

Candida Albicans ◽

Medical Devices ◽

Mammalian Cells ◽

Surface Engineering ◽

Pathogenic Yeast ◽

Bioactive Coatings ◽

Clinical Strains ◽

Persistent Infections ◽

Compound Q ◽

Significant Step

Currently there is a gap between the rate of new antifungal development and the emergence of resistance among Candida clinical strains, particularly threatened by the extreme adhesiveness of C. albicans to indwelling medical devices. Two silver camphorimine complexes, [Ag(OH){OC10H14N(C6H4)2NC10H14O}] (compound P) and [{Ag(OC10H14NC6H4CH3-p)}2(μ-O)] (compound Q), are herein demonstrated as having high inhibiting activity towards the growth of Candida albicans and Candida glabrata clinical strains resistant to azoles, the frontline antifungals used in clinical practice. Compounds P and Q were also explored as bioactive coatings to prevent colonization by C. albicans and colonize the surface of indwelling medical devices, resulting in persistent infections. Functionalization of stainless steel with polycaprolactone (PCL) matrix embedded with compounds P or Q was reported for the first time to inhibit the colonization of C. albicans by 82% and 75%, respectively. The coating of PCL loaded with Q or P did not cause cytotoxic effects in mammalian cells, demonstrating the biocompatibility of the explored approach. The identification and further exploration of new approaches for surface engineering based on new molecules that can sensitize resistant strains, as herein demonstrated for complexes P and Q, is a significant step forward to improve the successful treatment of candidiasis.

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Predicting high‐frequency variation in stream solute concentrations with water quality sensors and machine learning

Hydrological Processes ◽

10.1002/hyp.14000 ◽

2020 ◽

Author(s):

Mark B. Green ◽

Linda H. Pardo ◽

Scott W. Bailey ◽

John L. Campbell ◽

William H. McDowell ◽

...

Keyword(s):

Machine Learning ◽

Water Quality ◽

High Frequency ◽

Frequency Variation ◽

Water Quality Sensors

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The Inflammatory Response Induced by Aspartic Proteases of Candida albicans Is Independent of Proteolytic Activity

Infection and Immunity ◽

10.1128/iai.00789-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4754-4762 ◽

Cited By ~ 35

Author(s):

Donatella Pietrella ◽

Anna Rachini ◽

Neelam Pandey ◽

Lydia Schild ◽

Mihai Netea ◽

...

Keyword(s):

Candida Albicans ◽

Inflammatory Response ◽

Proteolytic Activity ◽

Necrosis Factor Alpha ◽

Pathogenic Yeast ◽

Aspartic Proteases ◽

Akt Activation ◽

Tnf Α ◽

Factor Alpha ◽

Pepstatin A

ABSTRACT The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast Candida albicans. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca2+ influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of C. albicans with the host.

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Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases.

Journal of Experimental Medicine ◽

10.1084/jem.183.1.323 ◽

1996 ◽

Vol 183 (1) ◽

pp. 323-327 ◽

Cited By ~ 85

Author(s):

Q L Yang ◽

E C Gotschlich

Keyword(s):

Sequence Analysis ◽

Neisseria Gonorrhoeae ◽

Experimental Evidence ◽

High Frequency ◽

Genetic Mechanism ◽

Frequency Variation ◽

Alpha Chain ◽

Glycosyl Transferases ◽

Genes Encoding

The lipooligosaccharide (LOS) expressed by gonococci spontaneously varies its structure at high frequency, but the underlying genetic mechanism has not been described. We have previously reported that the genes encoding the glycosyl transferases responsible for the biosynthesis of the variable alpha chain of the LOS of Neisseria gonorrhoeae are located in a locus containing five genes, lgtA, lgtB, lgtC, lgtD, and lgtE. Sequence analysis showed that lgtA, lgtC, and lgtD contained poly-G tracts within the coding frames, leading to the hypothesis that shifts in the number of guanosine residues in the poly-G tracts might be responsible for the high frequency variation in structure of gonococcal LOS. We now provide experimental evidence confirming this hypothesis.

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Farnesol restores wild-type colony morphology to 96% of Candida albicans colony morphology variants recovered following treatment with mutagens

Genome ◽

10.1139/g05-117 ◽

2006 ◽

Vol 49 (4) ◽

pp. 346-353 ◽

Cited By ~ 9

Author(s):

Ellen C Jensen ◽

Jacob M Hornby ◽

Nicole E Pagliaccetti ◽

Chuleeon M Wolter ◽

Kenneth W Nickerson ◽

...

Keyword(s):

Candida Albicans ◽

Quorum Sensing ◽

Environmental Conditions ◽

Budding Yeast ◽

Colony Morphology ◽

Morphological Transition ◽

Strongly Correlated ◽

Wild Type ◽

Hyphal Morphology

Candida albicans is a diploid fungus that undergoes a morphological transition between budding yeast, hyphal, and pseudohyphal forms. The morphological transition is strongly correlated with virulence and is regulated in part by quorum sensing. Candida albicans produces and secretes farnesol that regulates the yeast to mycelia morphological transition. Mutants that fail to synthesize or respond to farnesol could be locked in the filamentous mode. To test this hypothesis, a collection of C. albicans mutants were isolated that have altered colony morphologies indicative of the presence of hyphal cells under environmental conditions where C. albicans normally grows only as yeasts. All mutants were characterized for their ability to respond to farnesol. Of these, 95.9% fully or partially reverted to wild-type morphology on yeast malt (YM) agar plates supplemented with farnesol. All mutants that respond to farnesol regained their hyphal morphology when restreaked on YM plates without farnesol. The observation that farnesol remedial mutants are so common (95.9%) relative to mutants that fail to respond to farnesol (4.1%) suggests that farnesol activates and (or) induces a pathway that can override many of the morphogenesis defects in these mutants. Additionally, 9 mutants chosen at random were screened for farnesol production. Two mutants failed to produce detectable levels of farnesol.Key words: farnesol-remedial mutants, farnesol-sensing mutants, farnesol-synthesis mutants, quorum sensing, Candida albicans, morphological transition.

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Frequency variations of gravity waves interacting with a time-varying tide

Annales Geophysicae ◽

10.5194/angeo-31-1731-2013 ◽

2013 ◽

Vol 31 (10) ◽

pp. 1731-1743 ◽

Cited By ~ 7

Author(s):

C. M. Huang ◽

S. D. Zhang ◽

F. Yi ◽

K. M. Huang ◽

Y. H. Zhang ◽

...

Keyword(s):

Gravity Waves ◽

High Frequency ◽

Lower Atmosphere ◽

Horizontal Wind ◽

Frequency Variation ◽

Time Varying ◽

Transient Nature ◽

Critical Layers ◽

Favorable Conditions ◽

Frequency Variations

Abstract. Using a nonlinear, 2-D time-dependent numerical model, we simulate the propagation of gravity waves (GWs) in a time-varying tide. Our simulations show that when a GW packet propagates in a time-varying tidal-wind environment, not only its intrinsic frequency but also its ground-based frequency would change significantly. The tidal horizontal-wind acceleration dominates the GW frequency variation. Positive (negative) accelerations induce frequency increases (decreases) with time. More interestingly, tidal-wind acceleration near the critical layers always causes the GW frequency to increase, which may partially explain the observations that high-frequency GW components are more dominant in the middle and upper atmosphere than in the lower atmosphere. The combination of the increased ground-based frequency of propagating GWs in a time-varying tidal-wind field and the transient nature of the critical layer induced by a time-varying tidal zonal wind creates favorable conditions for GWs to penetrate their originally expected critical layers. Consequently, GWs have an impact on the background atmosphere at much higher altitudes than expected, which indicates that the dynamical effects of tidal–GW interactions are more complicated than usually taken into account by GW parameterizations in global models.

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