scholarly journals Deletion of the SKO1 Gene in a hog1 Mutant Reverts Virulence in Candida albicans

2019 ◽  
Vol 5 (4) ◽  
pp. 107
Author(s):  
Verónica Urrialde ◽  
Daniel Prieto ◽  
Susana Hidalgo-Vico ◽  
Elvira Román ◽  
Jesús Pla ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Intestinal Tract ◽  
Galleria Mellonella ◽  
Ex Vivo ◽  
Mutant Cell ◽  
Systemic Infection ◽  
Infection Model ◽  
Relevant Role

Candida albicans displays the ability to adapt to a wide variety of environmental conditions, triggering signaling pathways and transcriptional regulation. Sko1 is a transcription factor that was previously involved in early hypoxic response, cell wall remodeling, and stress response. In the present work, the role of sko1 mutant in in vivo and ex vivo studies was explored. The sko1 mutant behaved as its parental wild type strain regarding the ability to colonize murine intestinal tract, ex vivo adhesion to murine gut epithelium, or systemic virulence. These observations suggest that Sko1 is expendable during commensalism or pathogenesis. Nevertheless, the study of the hog1 sko1 double mutant showed unexpected phenotypes. Previous researches reported that the deletion of the HOG1 gene led to avirulent C. albicans mutant cell, which was, therefore, unable to establish as a commensal in a gastrointestinal murine model. Here, we show that the deletion of sko1 in a hog1 background reverted the virulence of the hog1 mutant in a systemic infection model in Galleria mellonella larvae and slightly improved the ability to colonize the murine gut in a commensalism animal model compared to the hog1 mutant. These results indicate that Sko1 acts as a repressor of virulence related genes, concluding that Sko1 plays a relevant role during commensalism and systemic infection.

scholarly journals Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model

2015 ◽  
Vol 14 (8) ◽  
pp. 834-844 ◽  
Author(s):  
Ranjith Rajendran ◽  
Elisa Borghi ◽  
Monica Falleni ◽  
Federica Perdoni ◽  
Delfina Tosi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Inflammatory Responses ◽  
Fungal Infections ◽  
Infection Model ◽  
Content Type

ABSTRACT Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo . In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.

scholarly journals Minimal Inhibitory Concentration (MIC)-Phenomena in Candida albicans and Their Impact on the Diagnosis of Antifungal Resistance

2019 ◽  
Vol 5 (3) ◽  
pp. 83 ◽  
Author(s):  
Ulrike Binder ◽  
Maria Aigner ◽  
Brigitte Risslegger ◽  
Caroline Hörtnagl ◽  
Cornelia Lass-Flörl ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Treatment Response ◽  
Minimal Inhibitory Concentration ◽  
Antifungal Therapy ◽  
Inhibitory Concentration ◽  
Galleria Mellonella ◽  
Antifungal Susceptibility ◽  
Infection Model ◽  
The Impact

Antifungal susceptibility testing (AFST) of clinical isolates is a tool in routine diagnostics to facilitate decision making on optimal antifungal therapy. The minimal inhibitory concentration (MIC)-phenomena (trailing and paradoxical effects (PXE)) observed in AFST complicate the unambiguous and reproducible determination of MICs and the impact of these phenomena on in vivo outcome are not fully understood. We aimed to link the MIC-phenomena with in vivo treatment response using the alternative infection model Galleria mellonella. We found that Candida albicans strains exhibiting PXE for caspofungin (CAS) had variable treatment outcomes in the Galleria model. In contrast, C. albicans strains showing trailing for voriconazole failed to respond in vivo. Caspofungin- and voriconazole-susceptible C. albicans strains responded to the respective antifungal therapy in vivo. In conclusion, MIC data and subsequent susceptibility interpretation of strains exhibiting PXE and/or trailing should be carried out with caution, as both effects are linked to drug adaptation and treatment response is uncertain to predict.

scholarly journals Anti-adhesive and anti-biofilm activity of NC-E08. In vitro and in vivo study using Galleria mellonella infection model

2019 ◽  
Author(s):  
Gabriela Fernanda Bombarda ◽  
Janaina de Cássia Orlandi Sardi ◽  
Pedro L. Rosalen ◽  
Josy G. Lazarini ◽  
Eder R. Paganini ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Early Childhood Caries ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Oral Diseases ◽  
Antimicrobial Drugs ◽  
Structural Analogues

Biofilms are organized microbial communities formed from an ecological succession. Biofilm formation functions as a mechanism of virulence and favors the development of diseases, including oral diseases such as dental caries and periodontal disease, in which the microorganisms Streptococcus mutans and Candida albicans are closely related. Previous studies have shown that interactions between S. mutans and C. albicans are associated with the pathogenesis of early childhood caries (ECC). Therefore, there is a great interest in finding new prototypes for antimicrobial drugs, mainly for the development of structural analogues of chalcones, which constitute one of the largest classes of natural products belonging to the flavonoid family and are considered strategic molecules for this purpose.

scholarly journals Haemoperfused liver as an ex vivo model for organ invasion of Candida albicans

2007 ◽  
Vol 56 (2) ◽  
pp. 266-270 ◽  
Author(s):  
Sascha Thewes ◽  
Hilde-Kristin Reed ◽  
Christian Grosse-Siestrup ◽  
David A. Groneberg ◽  
Michael Meissler ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Time Course ◽  
Ex Vivo ◽  
Infection Model ◽  
Ex Vivo Model ◽  
Human Fungal Pathogen ◽  
Non Invasive ◽  
Successful Establishment ◽  
Set Up

To study invasion of the human fungal pathogen Candida albicans, several infection models have been established. This study describes the successful establishment of an ex vivo haemoperfused liver as a model to study invasion of C. albicans. Perfused organs from pigs could be kept functional for up to 12 h. By comparing a non-invasive and invasive strain of C. albicans and by following a time course of invasion, it was shown that the invasion process in the perfused liver infection model is very similar to the in vivo situation after intraperitoneal infection of mice. The advantage of this set-up compared with other models of invasion is discussed.

scholarly journals Antibacterial Activity of a Promising Antibacterial Agent: 22-(4-(2-(4-Nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3502
Author(s):  
Xiang-Yi Zuo ◽  
Hong Gao ◽  
Mei-Ling Gao ◽  
Zhen Jin ◽  
You-Zhi Tang
Keyword(s):  
Antibacterial Activity ◽  
Galleria Mellonella ◽  
Systemic Infection ◽  
Effect Study ◽  
Infection Model ◽  
Oral Toxicity ◽  
Reference Drug ◽  
Antibiotic Effect

A novel pleuromutilin derivative, 22-(4-(2-(4-nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin (NPDM), was synthesized in our laboratory and proved excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, more methods were used to further study its preliminary pharmacological effect. The antibacterial efficacy and toxicity of NPDM were evaluated using tiamulin as the reference drug. The in vitro antibacterial activity study showed that NPDM is a potent bactericidal agent against MRSA that induced time-dependent growth inhibition and a concentration-dependent post-antibiotic effect (PAE). Toxicity determination showed that the cytotoxicity of NPDM was slightly higher than that of tiamulin, but the acute oral toxicity study proved that NPDM was a low-toxic compound. In an in vivo antibacterial effect study, NPDM exhibited a better therapeutic effect than tiamulin against MRSA in a mouse thigh infection model as well as a mouse systemic infection model with neutropenia. The 50% effective dose (ED50) of NPDM in a Galleria mellonella infection model was 50.53 mg/kg. The pharmacokinetic properties of NPDM were also measured, which showed that NPDM was a rapid elimination drug in mice.

scholarly journals Type VI secretion system and its effectors PdpC, PdpD and OpiA contribute to Francisella virulence in Galleria mellonella larvae

2021 ◽  
Author(s):  
Maj Brodmann ◽  
Sophie Schnider ◽  
Marek Basler
Keyword(s):  
Galleria Mellonella ◽  
Response Regulator ◽  
Infection Model ◽  
Type Vi Secretion System ◽  
Infectious Dose ◽  
Infection Models

Francisella tularensis causes the deadly zoonotic disease tularemia in humans and is able to infect a broad range of organisms including arthropods, which are thought to play a major role in Francisella transmission. However, while mammalian in vitro and in vivo infection models are widely used to investigate Francisella pathogenicity, a detailed characterization of the major Francisella virulence factor, a non-canonical T6SS, in an arthropod in vivo infection model is missing. Here we use Galleria mellonella larvae to analyze the role of the Francisella T6SS and its corresponding effectors in F. novicida virulence. We report that G. mellonella larvae killing depends on the functional T6SS and infectious dose. In contrast to other mammalian in vivo infection models, even one of PdpC, PdpD or OpiA T6SS effectors is sufficient to kill G. mellonella larvae while sheath recycling by ClpB is dispensable. We further demonstrate that treatment by polyethylene glycol (PEG) activates Francisella T6SS in liquid culture and that this is independent of the response regulator PmrA. PEG-activated IglC secretion is dependent on T6SS structural component PdpB but independent of putative effectors PdpC, PdpD, AnmK and OpiB1-3. The results of larvae infection and secretion assay suggest that AnmK, a putative T6SS component with unknown function, interferes with OpiA-mediated toxicity but not with general T6SS activity. We establish that the easy-to-use G. mellonella larvae infection model provides new insights into function of T6SS and pathogenesis of Francisella.

scholarly journals RNA Enrichment Method for Quantitative Transcriptional Analysis of Pathogens In Vivo Applied to the Fungus Candida albicans

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
Sara Amorim-Vaz ◽  
Van Du T. Tran ◽  
Sylvain Pradervand ◽  
Marco Pagni ◽  
Alix T. Coste ◽  
...  
Keyword(s):  
Candida Albicans ◽  
High Resolution ◽  
Galleria Mellonella ◽  
Iron Acquisition ◽  
Transcriptional Response ◽  
Systemic Infection ◽  
Microbial Pathogens ◽  
Transcriptional Analysis ◽  
Content Type

ABSTRACT In vivo transcriptional analyses of microbial pathogens are often hampered by low proportions of pathogen biomass in host organs, hindering the coverage of full pathogen transcriptome. We aimed to address the transcriptome profiles of Candida albicans, the most prevalent fungal pathogen in systemically infected immunocompromised patients, during systemic infection in different hosts. We developed a strategy for high-resolution quantitative analysis of the C. albicans transcriptome directly from early and late stages of systemic infection in two different host models, mouse and the insect Galleria mellonella. Our results show that transcriptome sequencing (RNA-seq) libraries were enriched for fungal transcripts up to 1,600-fold using biotinylated bait probes to capture C. albicans sequences. This enrichment biased the read counts of only ~3% of the genes, which can be identified and removed based on a priori criteria. This allowed an unprecedented resolution of C. albicans transcriptome in vivo, with detection of over 86% of its genes. The transcriptional response of the fungus was surprisingly similar during infection of the two hosts and at the two time points, although some host- and time point-specific genes could be identified. Genes that were highly induced during infection were involved, for instance, in stress response, adhesion, iron acquisition, and biofilm formation. Of the in vivo-regulated genes, 10% are still of unknown function, and their future study will be of great interest. The fungal RNA enrichment procedure used here will help a better characterization of the C. albicans response in infected hosts and may be applied to other microbial pathogens. IMPORTANCE Understanding the mechanisms utilized by pathogens to infect and cause disease in their hosts is crucial for rational drug development. Transcriptomic studies may help investigations of these mechanisms by determining which genes are expressed specifically during infection. This task has been difficult so far, since the proportion of microbial biomass in infected tissues is often extremely low, thus limiting the depth of sequencing and comprehensive transcriptome analysis. Here, we adapted a technology to capture and enrich C. albicans RNA, which was next used for deep RNA sequencing directly from infected tissues from two different host organisms. The high-resolution transcriptome revealed a large number of genes that were so far unknown to participate in infection, which will likely constitute a focus of study in the future. More importantly, this method may be adapted to perform transcript profiling of any other microbes during host infection or colonization.

scholarly journals Rapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christine Dunker ◽  
Melanie Polke ◽  
Bianca Schulze-Richter ◽  
Katja Schubert ◽  
Sven Rudolphi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Systemic Infection ◽  
Hyphal Growth ◽  
Metabolic Adaptation ◽  
Infection Model ◽  
Intraperitoneal Infection ◽  
Systemic Infections

AbstractThe ability of the fungal pathogen Candida albicans to undergo a yeast-to-hypha transition is believed to be a key virulence factor, as filaments mediate tissue damage. Here, we show that virulence is not necessarily reduced in filament-deficient strains, and the results depend on the infection model used. We generate a filament-deficient strain by deletion or repression of EED1 (known to be required for maintenance of hyphal growth). Consistent with previous studies, the strain is attenuated in damaging epithelial cells and macrophages in vitro and in a mouse model of intraperitoneal infection. However, in a mouse model of systemic infection, the strain is as virulent as the wild type when mice are challenged with intermediate infectious doses, and even more virulent when using low infectious doses. Retained virulence is associated with rapid yeast proliferation, likely the result of metabolic adaptation and improved fitness, leading to high organ fungal loads. Analyses of cytokine responses in vitro and in vivo, as well as systemic infections in immunosuppressed mice, suggest that differences in immunopathology contribute to some extent to retained virulence of the filament-deficient mutant. Our findings challenge the long-standing hypothesis that hyphae are essential for pathogenesis of systemic candidiasis by C. albicans.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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