Virulence of “white-gray-opaque” tri-stable transformation in clinical Candida albicans in vitro and in vivo

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

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The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04228-14 ◽

2014 ◽

Vol 59 (2) ◽

pp. 1341-1343 ◽

Cited By ~ 14

Author(s):

Nathan P. Wiederhold ◽

Laura K. Najvar ◽

Annette W. Fothergill ◽

Rosie Bocanegra ◽

Marcos Olivo ◽

...

Keyword(s):

Body Weight ◽

Candida Albicans ◽

Invasive Candidiasis ◽

Placebo Control ◽

The Novel ◽

Content Type ◽

Fungal Burden ◽

Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

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Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and ReducesIn VivoPathogenicity

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01451-12 ◽

2012 ◽

Vol 57 (1) ◽

pp. 445-451 ◽

Cited By ~ 41

Author(s):

Ilka Tiemy Kato ◽

Renato Araujo Prates ◽

Caetano Padial Sabino ◽

Beth Burgwyn Fuchs ◽

George P. Tegos ◽

...

Keyword(s):

Candida Albicans ◽

Virulence Factors ◽

Sodium Dodecyl ◽

Systemic Infection ◽

Tube Formation ◽

Photodynamic Inactivation ◽

Content Type ◽

Daughter Cells

ABSTRACTThe objective of this study was to evaluate whetherCandida albicansexhibits altered pathogenicity characteristics following sublethal antimicrobial photodynamic inactivation (APDI) and if such alterations are maintained in the daughter cells.C. albicanswas exposed to sublethal APDI by using methylene blue (MB) as a photosensitizer (0.05 mM) combined with a GaAlAs diode laser (λ 660 nm, 75 mW/cm2, 9 to 27 J/cm2).In vitro, we evaluated APDI effects onC. albicansgrowth, germ tube formation, sensitivity to oxidative and osmotic stress, cell wall integrity, and fluconazole susceptibility.In vivo, we evaluatedC. albicanspathogenicity with a mouse model of systemic infection. Animal survival was evaluated daily. Sublethal MB-mediated APDI reduced the growth rate and the ability ofC. albicansto form germ tubes compared to untreated cells (P< 0.05). Survival of mice systemically infected withC. albicanspretreated with APDI was significantly increased compared to mice infected with untreated yeast (P< 0.05). APDI increasedC. albicanssensitivity to sodium dodecyl sulfate, caffeine, and hydrogen peroxide. The MIC for fluconazole forC. albicanswas also reduced following sublethal MB-mediated APDI. However, none of those pathogenic parameters was altered in daughter cells ofC. albicanssubmitted to APDI. These data suggest that APDI may inhibit virulence factors and reducein vivopathogenicity ofC. albicans. The absence of alterations in daughter cells indicates that APDI effects are transitory. The MIC reduction for fluconazole following APDI suggests that this antifungal could be combined with APDI to treatC. albicansinfections.

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Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

Medical Mycology ◽

10.1093/mmy/myab054 ◽

2021 ◽

Author(s):

Rodrigo L Fabri ◽

Jhamine C O Freitas ◽

Ari S O Lemos ◽

Lara M Campos ◽

Irley O M Diniz ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Antifungal Activity ◽

Cell Membrane ◽

Multidrug Resistant ◽

Fungal Strain ◽

Vulvovaginal Candidiasis ◽

Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

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Candida Albicans — Platelet Interaction: Evidence for, in Vivo and in Vitro, Cell to Cell Attachment

Candida and Candidamycosis ◽

10.1007/978-1-4684-5910-4_18 ◽

1991 ◽

pp. 131-135 ◽

Cited By ~ 2

Author(s):

C. Mahaza ◽

R. Robert ◽

M. Miègeville ◽

G. Tronchin ◽

J. M. Senet

Keyword(s):

Candida Albicans ◽

Cell Attachment

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Germ Tubes and Proteinase Activity Contribute to Virulence of Candida albicans in Murine Peritonitis

Infection and Immunity ◽

10.1128/iai.67.12.6637-6642.1999 ◽

1999 ◽

Vol 67 (12) ◽

pp. 6637-6642 ◽

Cited By ~ 56

Author(s):

Marianne Kretschmar ◽

Bernhard Hube ◽

Thomas Bertsch ◽

Dominique Sanglard ◽

Renate Merker ◽

...

Keyword(s):

Candida Albicans ◽

Bowel Perforation ◽

Tube Length ◽

Triple Mutant ◽

Liver And Pancreas ◽

Organ Specific ◽

Secreted Aspartyl Proteinase ◽

Pepstatin A

ABSTRACT Peritonitis with Candida albicans is an important complication of bowel perforation and continuous ambulatory peritoneal dialysis. To define potential virulence factors, we investigated 50 strains of C. albicans in a murine peritonitis model. There was considerable variation in their virulence in this model when virulence was measured as release of organ-specific enzymes into the plasma of infected mice. Alanine aminotransferase (ALT) and α-amylase (AM) were used as parameters for damage of the liver and pancreas, respectively. The activities of ALT and AM in the plasma correlated with invasion into the organs measured in histologic sections and the median germ tube length induced with serum in vitro. When the activity of proteinases was inhibited in vivo with pepstatin A, there was a significant reduction of ALT and AM activities. This indicates that proteinases contributed to virulence in this model. Using strains ofC. albicans with disruption of secreted aspartyl proteinase gene SAP1, SAP2, SAP3, orSAP4 through SAP6 (collectively referred to asSAP4-6), we showed that only a Δsap4-6 triple mutant induced a significantly reduced activity of ALT in comparison to the reference strain. In contrast to the Δsap1, Δsap2, and Δsap3 mutants, the ALT induced by the Δsap4-6 mutant could not be further reduced by pepstatin A treatment, which indicates that Sap4-6 may contribute to virulence in this model.

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Evaluation du potentiel antimicrobien et de la toxicité des extraits de Jatropha multifida Linn, (Euphorbiaceae)

Journal of Applied Biosciences ◽

10.35759/jabs.151.4 ◽

2020 ◽

Vol 151 ◽

pp. 15550-15558

Author(s):

Amégninou Agban ◽

Yao Hoekou ◽

Passimna Pissang ◽

Tchadjobo Tchacondo ◽

Komlan Batawila

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Candida Albicans ◽

Aqueous Extract ◽

E Coli ◽

Toxicological Studies ◽

Jatropha Multifida

Objectif : L’objectif de ce travail était d’évaluer in vitro l’activité antimicrobienne des extraits de feuilles et tige de Jatropha multifida sur la croissance de Candida albicans, Escherichia coli et Staphylococcus aureus, puis d’évaluer in vivo la toxicité de cette plante. Méthodologie et résultats : Les méthodes de diffusion en milieu gélosé et de microdilution en milieu liquide ont été utilisées pour évaluer l’effet antimicrobien. Une étude en subaigüe était réalisée afin d’explorer les effets toxiques de l’extrait aqueux des feuilles. Les résultats des tests antimicrobiens montrent une activité des extraits de feuilles et tige de J. multifida sur la croissance des souches utilisées avec des diamètres de zones d’inhibition allant de 8 à 25 mm et des concentrations minimales inhibitrices (CMI) variant de 0,039 mg/mL à 1,25 mg/mL à l’exception des souches de E. coli qui sont résistantes aux extraits de la tige. L’administration en subaigüe de l’extrait aqueux des feuilles de J. multifida à la dose de 600 mg/kg entraîne une perte significative de poids chez les souris. Conclusion et applications des résultats : Les extraits aqueux, éthanolique et hydroéthanolique des feuilles et tige de J. multifida possèdent d’activité antimicrobienne et pourraient être utilisés dans le traitement des Candidoses à C. albicans et des infections à S. aureus. Mais l’essai de toxicité subaigüe montre que l’extrait aqueux de la plante serait toxique. Des études toxicologiques approfondies restent donc nécessaires sur ces extraits afin de mieux élucider leur inocuité. Mots-clés : Jatropha multifida, extraits de feuilles et de tige, activités antifongique et antibactérienne, toxicité. Agban et al., J. Appl. Biosci. 2020 Evaluation du potentiel antimicrobien et de la toxicité des extraits de Jatropha multifida Linn, (Euphorbiaceae) 15551 Evaluation of antimicrobial potential and toxicity of Jatropha multifida Linn, (Euphorbiaceae) extracts ABSTRACT Objective: The objective of this study was to evaluate in vitro the antimicrobial activity of leaves and stem of Jatropha multifida extracts against Candida albicans, Escherichia coli and Staphylococcus aureus, and then to evaluate in vivo the toxicity of this plant. Methodology and Results: The agar well-diffusion and the NCCLS broth microdilution methods were used to assess the antimicrobial effect. A subacute study was carried out to explore the toxic effects of the aqueous extract of the leaves. The results of the antimicrobial tests show an activity of the extracts of leaves and stems of J. multifida on the growth of the strains used with diameters of inhibitory zones ranging from 8 to 25 mm and minimum inhibitory concentrations (MIC) varying from 0.039 mg/mL to 1.25 mg/mL exception E. coli strains which are resistant to extracts from the stem. Subacute administration of the aqueous extract of the leaves of J. multifida at a dose of 600 mg/kg leads to a significant loss of weight in the mice. Conclusion and application of findings : The aqueous, ethanolic and hydroethanolic extracts of the leaves and stem of J. multifida have antimicrobial activity and could be used in the treatment of Candidiasis and bacterial infections due respectively to C. albicans and S. aureus. But the subacute toxicity test shows that the aqueous extract of the plant would be toxic. Extensive toxicological studies therefore remain necessary on these extracts in order to better elucidate their safety. Keywords: Jatropha multifida extracts of leaves and stem, antifungal and antibacterial activities, toxicity

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CAPACIDAD PROBIÓTICA DE BACTERIAS LÁCTICAS AISLADAS DE CHICHA DE MOLLE

Revista de la Sociedad Química del Perú ◽

10.37761/rsqp.v83i4.212 ◽

2017 ◽

Vol 83 (4) ◽

pp. 391-402

Author(s):

Jhanina Rodríguez Carrasco ◽

Paula García-Godos Alcázar

Keyword(s):

Escherichia Coli ◽

Candida Albicans ◽

Salmonella Typhimurium ◽

Lactobacillus Plantarum ◽

Leuconostoc Mesenteroides

La investigación tuvo como objetivos aislar e identificar bacterias lácticas (BAL), evaluar la capacidad probiótica in vitro e in vivo de bacterias lácticas aisladas de chicha de molle, para ello se muestreó chichas de molle elaboradas artesanalmente de las provincias de Huanta y Huamanga, aislando 55 cepas BAL e identificando a Lactobacillus plantarum, Lactobacillus maltaromicus y Leuconostoc mesenteroides en base a la coloración Gram, producción de gas, gluconato y fermentación de azúcares. Para evaluar la capacidad probiótica in vitro se realizaron pruebas de antagonismo entre BAL con cuatro microorganismos patógenos (Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028, Staphylococus aureus ATCC 25923 y Candida albicans ATCC 90028), mostrándose que 14 de las 55 cepas BAL producen sustancias inhibitorias de amplio espectro; asimismo, se evaluó la capacidad de tolerancia a condiciones gastrointestinales de cepas BAL, realizando ensayos a diferentes pHs , diferentes concentraciones de sales biliares y extracto gástrico artificial, resultando 25 cepas BAL con capacidad de tolerancia gastrointestinal y se seleccionaron cuatro cepas con mayor diámetro de halos de inhibición y cepas tolerantes a condiciones gastrointestinales siendo las cepas: BL-1 (Lactobacillus plantarum), BL-26 (Lactobacillus maltaromicus), BL-27 (Lactobacillus plantarum) y BL-53 (Lactobacillus maltaromicus), a las cuales se evaluaron la capacidad probiótica in vivo en 20 ratas para luego realizar recuento de BAL en el intestino a los 21 días, encontrándose en el grupo de estudio con BAL a 60x1019 UFC/ mL, mientras en el tratamiento con BAL más yacón a 25x1024 UFC/mL y los tratamientos de yacón y control a 50x1014 UFC/mL de BAL obteniéndose una de ganancia de peso en ratas en el grupo de estudio de BAL más yacón de 46 g, mientras con bacterias lácticas se tuvo 24 g y 16 g en el grupo control y extracto de yacón. En consecuencia esta investigación demuestra que la toma diaria de bebidas fermentadas tradicionales favorece el incremento de Lactobacillus en la microbiota intestinal.

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