Virulence of the Fungal Pathogen Candida albicans Requires the Five Isoforms of Protein Mannosyltransferases

ABSTRACT The PMT gene family in Candida albicans encodes five isoforms of protein mannosyltransferases (Pmt proteins Pmt1p, Pmt2p, Pmt4p, Pmt5p, and Pmt6p) that initiate O mannosylation of secretory proteins. We compared virulence characteristics of pmt mutants in two complex, three-dimensional models of localized candidiasis, using reconstituted human epithelium (RHE) and engineered human oral mucosa (EHOM); in addition, mutants were tested in a mouse model of hematogenously disseminated candidiasis (HDC). All pmt mutants showed attenuated virulence in the HDC model and at least one model of localized candidiasis. The pmt5 mutant, which lacks in vitro growth phenotypes, was less virulent in the EHOM and HDC assays but had no consistent phenotype in the RHE assay. In contrast, the pmt4 and pmt6 mutants were less virulent in the RHE and HDC assays but not in the EHOM assay. The results stress the contribution of all Pmt isoforms to the virulence of C. albicans and suggest that the importance of individual Pmt isoforms may differ in specific host niches. We propose that Pmt proteins may be suitable targets for future novel classes of antifungal agents.

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In vitroactivities of fluconazole, itraconazole and voriconazole against otomycotic fungal pathogens

The Journal of Laryngology & Otology ◽

10.1017/s0022215109005489 ◽

2009 ◽

Vol 123 (9) ◽

pp. 978-981 ◽

Cited By ~ 9

Author(s):

G Yenişehirli ◽

Y Bulut ◽

M Güven ◽

E Günday

Keyword(s):

Candida Albicans ◽

Minimum Inhibitory Concentration ◽

Fungal Pathogen ◽

Fungal Pathogens ◽

Antifungal Agents ◽

Inhibitory Concentration ◽

Fungal Isolate ◽

Test Method ◽

The Mean

AbstractObjective:To determine the causative pathogens of otomycosis, and to evaluate thein vitroactivity of antifungal agents against these pathogens.Materials and methods:A total of 96 fungal isolate were taken from 92 patients suspected of otomycosis. Thein vitroactivity of fluconazole, itraconazole and voriconazole against otomycotic pathogens was tested using the E-test method.Results:The most common pathogen wasAspergillus fumigatus(40.6 per cent), followed byA niger(35.4 per cent),A flavus(12.5 per cent) andCandida albicans(11.5 per cent). AllAspergillusspecies were found to be resistant to fluconazole (minimum inhibitory concentration ≥256 µg/ml). The mean minimum inhibitory concentrations of voriconazole forA fumigatus,A niger,A flavusandC albicanswere significantly lower than those of itraconazole for the same pathogens.Conclusion:This study found that the most common otomycotic fungal pathogen wasA fumigatus, and that voriconazole had more potentin vitroactivity than itraconazole against allAspergillusspecies as well as againstC albicans.

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Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

10.1101/2021.09.09.459426 ◽

2021 ◽

Author(s):

Joy Lachat ◽

Alice Pascault ◽

Delphine Thibaut ◽

Rémi Le Borgne ◽

Jean-Marc Verbavatz ◽

...

Keyword(s):

Candida Albicans ◽

Fungal Pathogen ◽

Single Cell Analysis ◽

Three Dimensional ◽

Systemic Infection ◽

Host Cells ◽

Galectin 3 ◽

Opportunistic Fungal Pathogen ◽

Epithelial Layers

SummaryThe opportunistic fungal pathogen Candida albicans is normally commensal, residing in the mucosa of most healthy individuals. In susceptible hosts, its filamentous hyphal form can invade epithelial layers leading to superficial or severe systemic infection. Invasion is mainly intracellular, though it causes no apparent damage to host cells. We investigated the invasive lifestyle of C. albicans in vitro using live-cell imaging and the damage-sensitive reporter galectin-3. Quantitative single cell analysis showed that invasion can result in host membrane breaching at different stages of invasion and cell death, or in traversal of host cells without membrane breaching. Membrane labelling and three-dimensional “volume” electron microscopy revealed that hyphae can traverse several host cells within trans-cellular tunnels that are progressively remodelled and may undergo ‘inflations’ linked to host glycogen stores, possibly during nutrient uptake. Thus, C. albicans invade epithelial tissues by either inflicting or avoiding host damage, the latter facilitated by trans-cellular tunnelling.

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Comparison between efficacy of allicin and fluconazole against Candida albicans in vitro and in a systemic candidiasis mouse model

FEMS Microbiology Letters ◽

10.1111/j.1574-6968.2010.02170.x ◽

2011 ◽

Vol 315 (2) ◽

pp. 87-93 ◽

Cited By ~ 20

Author(s):

Alireza Khodavandi ◽

Fahimeh Alizadeh ◽

Nabil S. Harmal ◽

Shiran M. Sidik ◽

Fauziah Othman ◽

...

Keyword(s):

Candida Albicans ◽

Mouse Model ◽

Systemic Candidiasis

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Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.39.7.1512 ◽

1995 ◽

Vol 39 (7) ◽

pp. 1512-1516 ◽

Cited By ~ 21

Author(s):

J. V. Martinez-Suarez ◽

J. L. Rodriguez-Tudela

Keyword(s):

Candida Albicans ◽

Antifungal Agents ◽

Vitro Activity ◽

In Vitro Activity

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Melanin Externalization in Candida albicans Depends on Cell Wall Chitin Structures

Eukaryotic Cell ◽

10.1128/ec.00051-10 ◽

2010 ◽

Vol 9 (9) ◽

pp. 1329-1342 ◽

Cited By ~ 55

Author(s):

Claire A. Walker ◽

Beatriz L. Gómez ◽

Héctor M. Mora-Montes ◽

Kevin S. Mackenzie ◽

Carol A. Munro ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Fungal Pathogen ◽

Cell Walls ◽

Chitin Synthesis ◽

Melanin Production ◽

Content Type ◽

Encoding Gene ◽

Chitinase Genes

ABSTRACT The fungal pathogen Candida albicans produces dark-pigmented melanin after 3 to 4 days of incubation in medium containing l-3,4-dihydroxyphenylalanine (l-DOPA) as a substrate. Expression profiling of C. albicans revealed very few genes significantly up- or downregulated by growth in l-DOPA. We were unable to determine a possible role for melanin in the virulence of C. albicans. However, we showed that melanin was externalized from the fungal cells in the form of electron-dense melanosomes that were free or often loosely bound to the cell wall exterior. Melanin production was boosted by the addition of N-acetylglucosamine to the medium, indicating a possible association between melanin production and chitin synthesis. Melanin externalization was blocked in a mutant specifically disrupted in the chitin synthase-encoding gene CHS2. Melanosomes remained within the outermost cell wall layers in chs3Δ and chs2Δ chs3Δ mutants but were fully externalized in chs8Δ and chs2Δ chs8Δ mutants. All the CHS mutants synthesized dark pigment at equivalent rates from mixed membrane fractions in vitro, suggesting it was the form of chitin structure produced by the enzymes, not the enzymes themselves, that was involved in the melanin externalization process. Mutants with single and double disruptions of the chitinase genes CHT2 and CHT3 and the chitin pathway regulator ECM33 also showed impaired melanin externalization. We hypothesize that the chitin product of Chs3 forms a scaffold essential for normal externalization of melanosomes, while the Chs8 chitin product, probably produced in cell walls in greater quantity in the absence of CHS2, impedes externalization.

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ANCD thrombectomy device: in vitro evaluation

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2019-014856 ◽

2019 ◽

Vol 12 (1) ◽

pp. 77-81 ◽

Cited By ~ 5

Author(s):

Sonia Sanchez ◽

Ignacio Cortiñas ◽

Helena Villanova ◽

Anna Rios ◽

Iñaki Galve ◽

...

Keyword(s):

Three Dimensional ◽

Treatment Strategies ◽

Local Flow ◽

Guide Catheter ◽

First Pass ◽

Thrombectomy Device ◽

The Mean ◽

Three Dimensional Models ◽

Number Of Passes

IntroductionEndovascular treatment of stroke, although highly effective, may fail to reach complete recanalization in around 20% of cases. The Advanced Thrombectomy System (ANCD) is a novel stroke thrombectomy device designed to reduce clot fragmentation and facilitate retrieval by inducing local flow arrest and allowing distal aspiration in combination with a stent retriever. We aimed to assess the preclinical efficacy of ANCD.MethodsSoft red blood cell (RBC)-rich (n=20/group) and sticky fibrin-rich (n=30/group) clots were used to create middle cerebral artery (MCA) occlusions in two vascular phantoms. Three different treatment strategies were tested: (1) balloon guide catheter + Solitaire (BGC+SR); (2) distal access catheter + SR (DAC+SR); and (3) ANCD+SR, until complete recanalization was achieved or to a maximum of three passes. The recanalization rate was determined after each pass.ResultsAfter one pass, ANCD+SR resulted in an increased recanalization rate (94%) for all clots together compared with BGC+SR (66%; p<0.01) or DAC+SR (80%; p=0.04). After the final pass the recanalization rate increased in all three groups but remained higher with ANCD+SR (100%) than with BGC+SR (74%; p<0.01) or DAC+SR (90%; p=0.02). The mean number of passes was lower with ANCD+SR (1.06) than with BGC+SR (1.46) or DAC+SR (1.25) (p=0.01). A logistic regression model adjusted for treatment arm, clot type, and model used showed that both RBC-rich clots (OR 8.1, 95% CI 1.6 to 13.5) and ANCD+SR (OR 3.9, 95% CI 1.01 to 15.8) were independent predictors of first-pass recanalization.ConclusionIn in vitro three-dimensional models replicating MCA-M1 occlusion, ANCD+SR showed significantly better recanalization rates in fewer passes than other commonly used combinations of devices.

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Two stages in three-dimensional in vitro growth of tissue generated by osteoblastlike cells

Biointerphases ◽

10.1116/1.3431524 ◽

2010 ◽

Vol 5 (2) ◽

pp. 45-52 ◽

Cited By ~ 34

Author(s):

Krishna P. Kommareddy ◽

Claudia Lange ◽

Monika Rumpler ◽

John W. C. Dunlop ◽

Inderchand Manjubala ◽

...

Keyword(s):

Three Dimensional ◽

In Vitro Growth ◽

Two Stages

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In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.10.2503 ◽

1998 ◽

Vol 42 (10) ◽

pp. 2503-2510 ◽

Cited By ~ 58

Author(s):

Maurizio Del Poeta ◽

Wiley A. Schell ◽

Christine C. Dykstra ◽

Susan K. Jones ◽

Richard R. Tidwell ◽

...

Keyword(s):

Antimicrobial Activity ◽

Candida Albicans ◽

Fusarium Solani ◽

Antifungal Agents ◽

Antifungal Drugs ◽

Inhibitory Compounds ◽

Wide Range ◽

Fluconazole Resistant ◽

Resistant Strains

ABSTRACT Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities againstCandida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active againstAspergillus fumigatus, Fusarium solani,Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents.

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The effect of temperature on in vitro germination and germ tube growth of urediniospores of Tranzschelia discolor

Australian Journal of Agricultural Research ◽

10.1071/ar9900479 ◽

1990 ◽

Vol 41 (3) ◽

pp. 479 ◽

Cited By ~ 6

Author(s):

PJ Ellison ◽

BR Cullis ◽

RW Bambach ◽

PF Kable

Keyword(s):

Germ Tube ◽

Three Dimensional ◽

Tube Growth ◽

Effect Of Temperature ◽

In Vitro Germination ◽

Three Dimensional Models ◽

C 30 ◽

Tranzschelia Discolor ◽

Germ Tube Growth

The effect of temperature on in vitro germination and germ tube growth of urediniospores of Tranzschelia discolor was studied over time under constant temperature conditions. Studies were carried out on 1% water agar in the dark at 3�C, 5�C, 8�C, 10�C, 15�C, 20�C, 25�C, 28�C, 30�C and 32�C. Germination was observed at all temperatures between 5 and 30'C, and occurred rapidly over most of this range. At 2 h, germination exceeded 80% at temperatures between 10 and 28�C, and this level was reached at 3 h at 8�C. Germination at 5 and 30�C was much reduced and at 7 h reached only 44% and 38% respectively. Germ tube growth occurred most vigorously at 15 and 20�C, reaching lengths in excess of 500 8m at 9 h. The optimum range was narrower than that for germination, and growth was reduced or poor at 8�C, 10�C, 25�C and 28�C, which were favourable temperatures for germination. Average germ tube lengths at 9 h at these temperatures were 55, 245, 273 and 62 8m, respectively. Three-dimensional models were derived relating germination and germ tube growth to time and temperature.

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