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Open AccessArticle

Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging

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Sanne Schrevens

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Dominique Sanglard

J. Fungi 2021, 7(10), 844; https://doi.org/10.3390/jof7100844 - 09 Oct 2021

Cited by 4 | Viewed by 2293

Abstract

Urinary tract infections (UTIs) are quite common and mainly caused by bacteria such as Escherichia coli. However, when patients have urinary catheters, fungal infections comprise up to 15% of these types of infections. Moreover, fungal UTIs have a high mortality, due to [...] Read more.

Urinary tract infections (UTIs) are quite common and mainly caused by bacteria such as Escherichia coli. However, when patients have urinary catheters, fungal infections comprise up to 15% of these types of infections. Moreover, fungal UTIs have a high mortality, due to rapid spreading of the fungi to the kidneys. Most fungal UTIs are caused by Candida species, among which Candida albicans and Candida glabrata are the most common. C. glabrata is an opportunistic pathogenic yeast, phylogenetically quite close to Saccharomyces cerevisiae. Even though it is commonly isolated from the urinary tract and rapidly acquires resistance to antifungals, its pathogenesis has not been studied extensively in vivo. In vivo studies require high numbers of animals, which can be overcome by the use of non-invasive imaging tools. One such tool, bioluminescence imaging, has been used successfully to study different types of C. albicans infections. For C. glabrata, only biofilms on subcutaneously implanted catheters have been imaged using this tool. In this work, we investigated the progression of C. glabrata UTIs from the bladder to the kidneys and the spleen. Furthermore, we optimized expression of a red-shifted firefly luciferase in C. glabrata for in vivo use. We propose the first animal model using bioluminescence imaging to visualize C. glabrata in mouse tissues. Additionally, this UTI model can be used to monitor antifungal activity in vivo over time. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessArticle

Inactivation of Dermatophytes Causing Onychomycosis Using Non-Thermal Plasma as a Prerequisite for Therapy

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J. Fungi 2021, 7(9), 715; https://doi.org/10.3390/jof7090715 - 31 Aug 2021

Cited by 4 | Viewed by 1665

Abstract

Following our previous study of the therapy of onychomycosis by non-thermal plasma (NTP) and nail hygiene and to obtain some prerequisite data of dermatophytes sensitivity, the dynamics of those inactivation by NTP plasma was monitored for various strains of Trichophyton iterdigitale, Trichophyton [...] Read more.

Following our previous study of the therapy of onychomycosis by non-thermal plasma (NTP) and nail hygiene and to obtain some prerequisite data of dermatophytes sensitivity, the dynamics of those inactivation by NTP plasma was monitored for various strains of Trichophyton iterdigitale, Trichophyton benhamiae, Trichophyton rubrum, and Microsporum canis. Three strains of each species on agar plates were exposed with plasma produced by a DC corona discharge in the point-to-ring arrangement in various time intervals. Although all strains were sufficiently sensitive to plasma action, significant differences were observed in their sensitivity and inactivation dynamics. These differences did not correlate with the species classification of individual strains, but could be assigned to four arbitrarily created types of strain response to NTP according to their sensitivity. These results indicate that the sensitivity to plasma is not an inherent property of the fungal species, but varies from strain to strain. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessArticle

The Vacuolar Morphogenesis Protein Vam6-Like Protein Vlp1 Is Required for Pathogenicity of Cryptococcus neoformans

by

Cheng-Li Fan

and

Tong-Bao Liu

J. Fungi 2021, 7(6), 418; https://doi.org/10.3390/jof7060418 - 27 May 2021

Cited by 6 | Viewed by 2253

Abstract

Cryptococcus neoformans is an encapsulated yeast pathogen that infects immunocompromised patients to cause fungal meningitis, resulting in hundreds of thousands of deaths each year. F-box protein Fbp1, the key component of the E3 ubiquitin ligase, plays a critical role in fungal development and [...] Read more.

Cryptococcus neoformans is an encapsulated yeast pathogen that infects immunocompromised patients to cause fungal meningitis, resulting in hundreds of thousands of deaths each year. F-box protein Fbp1, the key component of the E3 ubiquitin ligase, plays a critical role in fungal development and virulence in fungal pathogens. In this study, we identified a potential substrate of Fbp1, the vacuolar morphogenesis protein Vam6-like protein Vlp1, and evaluated its role in virulence in C. neoformans. Deletion or overexpression of the VLP1 gene results in abnormal capsule formation and melanin production of C. neoformans. Stress tolerance assay showed that the vlp1Δ mutant was sensitive to SDS and NaCl but not to CFW or Congo red, indicating that Vlp1 might regulate the cell membrane integrity in C. neoformans. Fungal virulence assay showed that Vlp1 was essential for the pathogenicity of C. neoformans, as vlp1Δ mutants are avirulent in the mouse systematic infection model of cryptococcosis. The progression of fungal infection revealed that the vlp1Δ mutants were gradually eliminated from the lungs of the mice after infection. Moreover, the vlp1Δ mutants showed a proliferation defect inside macrophages and a viability defect in the host complement system, which likely contributes to the virulence attenuation of the vlp1Δ mutants. In summary, our results revealed that the vacuolar morphogenesis protein Vam6-like protein Vlp1 is essential for the pathogenicity of C. neoformans. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessArticle

Genotype, Antifungal Susceptibility, and Virulence of Clinical South African Cryptococcus neoformans Strains from National Surveillance, 2005–2009

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J. Fungi 2021, 7(5), 338; https://doi.org/10.3390/jof7050338 - 27 Apr 2021

Cited by 6 | Viewed by 1905

Abstract

In South Africa, Cryptococcus neoformans is the most common cause of adult meningitis. We performed multi locus sequence typing and fluconazole susceptibility testing of clinical C. neoformans isolates collected from 251 South African patients with cryptococcosis through national surveillance from 2005 to 2009. [...] Read more.

In South Africa, Cryptococcus neoformans is the most common cause of adult meningitis. We performed multi locus sequence typing and fluconazole susceptibility testing of clinical C. neoformans isolates collected from 251 South African patients with cryptococcosis through national surveillance from 2005 to 2009. We examined the association between clinical characteristics of patients and genotype, and the effect of genotype on in-hospital mortality. We performed whole genome phylogenetic analysis of fifteen C. neoformans isolates with the molecular type VNB and tested their virulence in a Galleria mellonella model. Most isolates had the molecular type VNI (206/251, 82%), followed by VNII (25/251, 10%), VNB (15/251, 6%), and VNIV (5/251, 2%); 67 sequence types were identified. There were no differences in fluconazole minimum inhibitory concentration (MIC) values among molecular types and the majority of strains had low MIC values (MIC₅₀ of 1 µg/mL and MIC₉₀ of 4 µg/mL). Males were almost twice as likely of being infected with a non-VNI genotype (adjusted odds ratio [OR]: 1.65, 95% confidence interval [CI]: 0.25–10.99; p = 0.61). Compared to patients infected with a VNI genotype, those with a non-VNI genotype had a 50% reduced adjusted odds of dying in hospital (95% CI: 0.03–7.57; p = 0.62). However, for both these analyses, our estimates had wide confidence intervals spanning 1 with large p-values. Fifteen VNB strains were not as virulent in a G. mellonella larval model as the H99 reference strain. A majority of these VNB strains belonged to the VNBII clade and were very closely related by phylogenetic analysis. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessArticle

High Frequency of Enterocytozoon bieneusi Genotype WL12 Occurrence among Immunocompromised Patients with Intestinal Microsporidiosis

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Mohamed Amine Skhairia

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J. Fungi 2021, 7(3), 161; https://doi.org/10.3390/jof7030161 - 24 Feb 2021

Cited by 4 | Viewed by 2918

Abstract

Microsporidiosis is an emerging opportunistic infection causing severe digestive disorders in immunocompromised patients. The aim of this study was to investigate the prevalence of intestinal microsporidia carriage among immunocompromised patients hospitalized at a major hospital complex in the Tunis capital area, Tunisia (North [...] Read more.

Microsporidiosis is an emerging opportunistic infection causing severe digestive disorders in immunocompromised patients. The aim of this study was to investigate the prevalence of intestinal microsporidia carriage among immunocompromised patients hospitalized at a major hospital complex in the Tunis capital area, Tunisia (North Africa), and perform molecular epidemiology and population structure analyses of Enterocytozoon bieneusi, which is an emerging fungal pathogen. We screened 250 stool samples for the presence of intestinal microsporidia from 171 patients, including 81 organ transplant recipients, 73 Human Immunodeficiency Virus (HIV)-positive patients, and 17 patients with unspecified immunodeficiency. Using a nested PCR-based diagnostic approach for the detection of E. bieneusi and Encephalitozoon spp., we identified 18 microsporidia-positive patients out of 171 (10.5%), among which 17 were infected with E. bieneusi. Microsporidia-positive cases displayed chronic diarrhea (17 out of 18), which was associated more with HIV rather than with immunosuppression other than HIV (12 out of 73 versus 6 out of 98, respectively, p = 0.02) and correlated with extended hospital stays compared to microsporidia-negative cases (60 versus 19 days on average, respectively; p = 0.001). Strikingly, internal transcribed spacer (ITS)-based genotyping of E. bieneusi strains revealed high-frequency occurrence of ITS sequences that were identical (n = 10) or similar (with one single polymorphic site, n = 3) to rare genotype WL12. Minimum-spanning tree analyses segregated the 17 E. bieneusi infection cases into four distinct genotypic clusters and confirmed the high prevalence of genotype WL12 in our patient population. Phylogenetic analyses allowed the mapping of all 17 E. bieneusi strains to zoonotic group 1 (subgroups 1a and 1b/1c), indicating loose host specificity and raising public health concern. Our study suggests a probable common source of E. bieneusi genotype WL12 transmission and prompts the implementation of a wider epidemiological investigation. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessReview

Accounting for the Biological Complexity of Pathogenic Fungi in Phylogenetic Dating

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Hannah M. Edwards

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Johanna Rhodes

J. Fungi 2021, 7(8), 661; https://doi.org/10.3390/jof7080661 - 14 Aug 2021

Cited by 3 | Viewed by 2239

Abstract

In the study of pathogen evolution, temporal dating of phylogenies provides information on when species and lineages may have diverged in the past. When combined with spatial and epidemiological data in phylodynamic models, these dated phylogenies can also help infer where and when [...] Read more.

In the study of pathogen evolution, temporal dating of phylogenies provides information on when species and lineages may have diverged in the past. When combined with spatial and epidemiological data in phylodynamic models, these dated phylogenies can also help infer where and when outbreaks occurred, how pathogens may have spread to new geographic locations and/or niches, and how virulence or drug resistance has developed over time. Although widely applied to viruses and, increasingly, to bacterial pathogen outbreaks, phylogenetic dating is yet to be widely used in the study of pathogenic fungi. Fungi are complex organisms with several biological processes that could present issues with appropriate inference of phylogenies, clock rates, and divergence times, including high levels of recombination and slower mutation rates although with potentially high levels of mutation rate variation. Here, we discuss some of the key methodological challenges in accurate phylogeny reconstruction for fungi in the context of the temporal analyses conducted to date and make recommendations for future dating studies to aid development of a best practices roadmap in light of the increasing threat of fungal outbreaks and antifungal drug resistance worldwide. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessReview

The Consequences of Our Changing Environment on Life Threatening and Debilitating Fungal Diseases in Humans

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Norman van Rhijn

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Michael Bromley

J. Fungi 2021, 7(5), 367; https://doi.org/10.3390/jof7050367 - 07 May 2021

Cited by 30 | Viewed by 8344

Abstract

Human activities have significantly impacted the environment and are changing our climate in ways that will have major consequences for ourselves, and endanger animal, plant and microbial life on Earth. Rising global temperatures and pollution have been highlighted as potential drivers for increases [...] Read more.

Human activities have significantly impacted the environment and are changing our climate in ways that will have major consequences for ourselves, and endanger animal, plant and microbial life on Earth. Rising global temperatures and pollution have been highlighted as potential drivers for increases in infectious diseases. Although infrequently highlighted, fungi are amongst the leading causes of infectious disease mortality, resulting in more than 1.5 million deaths every year. In this review we evaluate the evidence linking anthropomorphic impacts with changing epidemiology of fungal disease. We highlight how the geographic footprint of endemic mycosis has expanded, how populations susceptible to fungal infection and fungal allergy may increase and how climate change may select for pathogenic traits and indirectly contribute to the emergence of drug resistance. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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Open AccessSystematic Review

Comparative Efficacy of Antifungal Agents Used in the Treatment of Oropharyngeal Candidiasis among HIV-Infected Adults: A Systematic Review and Network Meta-Analysis

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Shamala Gopal Rajadurai

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Mari Kannan Maharajan

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Sajesh K. Veettil

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Divya Gopinath

J. Fungi 2021, 7(8), 637; https://doi.org/10.3390/jof7080637 - 05 Aug 2021

Cited by 11 | Viewed by 2928

Abstract

The objective of this study was to assess the comparative efficacy and safety of different antifungal agents used for the treatment of oropharyngeal candidiasis (OPC) in adult patients with HIV. A systematic search was performed on the four major databases (Medline, Embase, CENTRAL [...] Read more.

The objective of this study was to assess the comparative efficacy and safety of different antifungal agents used for the treatment of oropharyngeal candidiasis (OPC) in adult patients with HIV. A systematic search was performed on the four major databases (Medline, Embase, CENTRAL and Scopus) to identify randomized controlled trials (RCTs) that evaluated the efficacy of antifungal agents in HIV patients with OPC. A network meta-analysis was performed from the data extracted from the selected studies. The agents were ranked according using surface under the cumulative ranking (SUCRA). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of evidence. A total of 15 trials were included in the quantitative analysis involving the data from a total of 2883 participants. Fluconazole was ranked as the most effective antifungal agent to achieve clinical cure (SUCRA = 0.87) in OPC followed by posaconazole and itraconazole. Posaconazole was ranked the most efficacious agent in achieving mycological cure (SUCRA = 0.81), followed by fluconazole. While nystatin was ranked the safest, the effect estimates of none of the other systemic antifungal agents were significantly higher than fluconazole. Based on the available evidence, fluconazole can be considered as the most effective drug in the treatment of OPC among HIV-infected adults and has a favorable safety profile, followed by posaconazole. Full article

(This article belongs to the Special Issue Fungal Pathogens and Human Health)

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