scholarly journals Unaltered Fungal Burden and Lethality in Human CEACAM1-Transgenic Mice During Candida albicans Dissemination and Systemic Infection

2019 ◽  
Vol 10 ◽  
Author(s):  
Esther Klaile ◽  
Mario M. Müller ◽  
Cristina Zubiría-Barrera ◽  
Saskia Brehme ◽  
Tilman E. Klassert ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Transgenic Mice ◽  
Systemic Infection ◽  
Fungal Burden

Impact of serial systemic infection on Candida albicans virulence factors

2020 ◽  
Vol 15 (13) ◽  
pp. 1249-1263
Author(s):  
Glaucia S Arita ◽  
Daniella R Faria ◽  
Karina M Sakita ◽  
Franciele AV Rodrigues-Vendramini ◽  
Isis RG Capoci ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Murine Model ◽  
Systemic Infection ◽  
Systemic Candidiasis ◽  
Fungal Burden ◽  
Histopathological Findings ◽  
Phenotypic Profile ◽  
Proteomic Data ◽  
Repeated Contact

Aim: To evaluate changes in virulence and pathogenicity approaches from Candida albicans after successive passages in a murine model of systemic candidiasis. Materials & methods: Phenotypic assays were performed using colonies recovered from animals infected serially, totalizing five passages. Results: A progressive infection was observed along the passages, with increased fungal burden and the presence of greater inflammatory areas in the histopathological findings. Recovered strains exhibited increased filamentation and biofilm abilities, along with modulation of phospholipase and proteinase activities. Conclusion: Repeated contact between yeast and host increased the expression of virulence factors. Furthermore, a correspondence between phenotypic profile and proteomic data obtained previously was observed.

scholarly journals Ibuprofen Potentiates theIn VivoAntifungal Activity of Fluconazole against Candida albicans Murine Infection

2015 ◽  
Vol 59 (7) ◽  
pp. 4289-4292 ◽  
Author(s):  
Sofia Costa-de-Oliveira ◽  
Isabel M. Miranda ◽  
Ana Silva-Dias ◽  
Ana P. Silva ◽  
Acácio G. Rodrigues ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Murine Model ◽  
Resistant Strain ◽  
Efflux Pump ◽  
Systemic Infection ◽  
New Approach ◽  
Content Type ◽  
Fungal Burden ◽  
Fluconazole Resistant

ABSTRACTCandida albicansis the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression.

scholarly journals Identification and Characterization of TUP1-Regulated Genes in Candida albicans

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Burkhard R Braun ◽  
W Steven Head ◽  
Ming X Wang ◽  
Alexander D Johnson
Keyword(s):  
Candida Albicans ◽  
Systemic Infection ◽  
Subtractive Hybridization ◽  
Filamentous Growth ◽  
Surface Proteins ◽  
Infection Model ◽  
Ferric Reductase ◽  
Pathogenesis Related Protein ◽  
Plant Pathogenesis ◽  
Rnase T2

Abstract TUP1 encodes a transcriptional repressor that negatively controls filamentous growth in Candida albicans. Using subtractive hybridization, we identified six genes, termed repressed by TUP1 (RBT), whose expression is regulated by TUP1. One of the genes (HWP1) has previously been characterized, and a seventh TUP1-repressed gene (WAP1) was recovered due to its high similarity to RBT5. These genes all encode secreted or cell surface proteins, and four out of the seven (HWP1, RBT1, RBT5, and WAP1) encode putatively GPI-modified cell wall proteins. The remaining three, RBT2, RBT4, and RBT7, encode, respectively, an apparent ferric reductase, a plant pathogenesis-related protein (PR-1), and a putative secreted RNase T2. The expression of RBT1, RBT4, RBT5, HWP1, and WAP1 was induced in wild-type cells during the switch from the yeast form to filamentous growth, indicating the importance of TUP1 in regulating this process and implicating the RBTs in hyphal-specific functions. We produced knockout strains in C. albicans for RBT1, RBT2, RBT4, RBT5, and WAP1 and detected no phenotypes on several laboratory media. However, two animal models for C. albicans infection, a rabbit cornea model and a mouse systemic infection model, revealed that rbt1Δ and rbt4Δ strains had significantly reduced virulence. TUP1 appears, therefore, to regulate many genes in C. albicans, a significant fraction of which are induced during filamentous growth, and some of which participate in pathogenesis.

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

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
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.

scholarly journals Antimicrobial Photodynamic Inactivation Inhibits Candida albicans Virulence Factors and ReducesIn VivoPathogenicity

2012 ◽  
Vol 57 (1) ◽  
pp. 445-451 ◽  
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.

scholarly journals An Internal Polarity Landmark Is Important for Externally Induced Hyphal Behaviors in Candida albicans

2008 ◽  
Vol 7 (4) ◽  
pp. 712-720 ◽  
Author(s):  
Alexandra Brand ◽  
Anjalee Vacharaksa ◽  
Catherine Bendel ◽  
Jennifer Norton ◽  
Paula Haynes ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Kidney Tissue ◽  
Systemic Infection ◽  
Cell Cortex ◽  
Environmental Cues ◽  
Growth Responses ◽  
Directional Growth ◽  
Internal Polarity ◽  
Hyphal Tip

ABSTRACT Directional growth is a function of polarized cells such as neurites, pollen tubes, and fungal hyphae. Correct orientation of the extending cell tip depends on signaling pathways and effectors that mediate asymmetric responses to specific environmental cues. In the hyphal form of the eukaryotic fungal pathogen Candida albicans, these responses include thigmotropism and galvanotropism (hyphal turning in response to changes in substrate topography and imposed electrical fields, respectively) and penetration into semisolid substrates. During vegetative growth in C. albicans, as in the model yeast Saccharomyces cerevisiae, the Ras-like GTPase Rsr1 mediates internal cellular cues to position new buds in a prespecified pattern on the mother cell cortex. Here, we demonstrate that Rsr1 is also important for hyphal tip orientation in response to the external environmental cues that induce thigmotropic and galvanotropic growth. In addition, Rsr1 is involved in hyphal interactions with epithelial cells in vitro and its deletion diminishes the hyphal invasion of kidney tissue during systemic infection. Thus, Rsr1, an internal polarity landmark in yeast, is also involved in polarized growth responses to asymmetric environmental signals, a paradigm that is different from that described for the homologous protein in S. cerevisiae. Rsr1 may thereby contribute to the pathogenesis of C. albicans infections by influencing hyphal tip responses triggered by interaction with host tissues.

scholarly journals Immunosuppressive effect of cyclosporin A on resistance to systemic infection with Candida albicans

1989 ◽  
Vol 30 (3) ◽  
pp. 183-192 ◽  
Author(s):  
A. Vecchiarelli ◽  
E. Cenci ◽  
P. Marconi ◽  
R. Rossi ◽  
C. Riccardi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cyclosporin A ◽  
Systemic Infection ◽  
Immunosuppressive Effect

scholarly journals Candida Albicans ERG11 Gene Polymorphism: Impact on Its In Vivo Virulence and Susceptibility to Fluconazole According to the Galleria Mellonella Model

2021 ◽  
Author(s):  
Marcel Patindoilba Sawadogo ◽  
Adama Zida ◽  
Issiaka Soulama ◽  
Samuel S Sermé ◽  
Thierry Kiswendsida Guiguemdé ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Reference Strain ◽  
Galleria Mellonella ◽  
Larval Mortality ◽  
Fungal Burden ◽  
Significant Difference ◽  
Strain Sc5314 ◽  
Resistant Strains

The aim of this study is to have an idea on the molecular mechanisms of C. albicans resistance to fluconazole in Burkina Faso, by studying the polymorphism of the ERG11 gene, and its implication in the C. albicans virulence and resistance in vivo according to the Galleria mellonella model; (2) Methods: Ten (10) clinical strains including, 5 resistant and 5 susceptible and 1 virulent and susceptible reference strain SC5314 are used. For the estimation of virulence, the larvae were inoculated with 10 &mu;L of C. albicans cell suspension at variable concentrations: 2,5.105, 5.105, 1.106, and 5.106 CFU/larva of each strain. For the in vivo efficacy study, fluconazole was administered at 1, 4 and 16 mg/kg respectively to G. mellonella larvae, after infection by inoculum 5.106 CFU / larvae of each strain; (3) Results: Six (6) non-silent mutations in the ERG11 gene (K143R, F145L, G307S, S405F, G448E, V456I on ERG11p) were found in 4 resistant isolates. Larval mortality depended on fungal burden and strain. The inoculum 5.106 CFU caused 100% mortality in 2 days for the 2 CAAL-1 and CAAL-2 strains carrying the F145L mutation, in 3 days for the reference strain SC5314, in 4 days for the ensemble of resistant strains, and in 5 days for the ensemble of susceptible strains. The comparison of the mortality due to the reference strain SC5314 CFU / larva and the average mortality due to the two mutant F145L strains, shows a significant difference (P &lt;0.05).Fluconazole significantly protected (P&gt; 0.05) the larvae from infection by susceptible strains and the reference strain. However, 100% mortality in 6 days after injection of the resistant strains, was observed (4) Conclusions: Certain mutations in the ERG11 gene such as the F145L mutation are thought to be a source of increased virulence in Candida albicans. Fluconazole effectively protected larvae from infection by susceptible strains in vivo, unlike resistant strain

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