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J. Fungi, Volume 4, Issue 3 (September 2018)

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Open AccessArticle Molecular Identification, Antifungal Susceptibility, and Geographic Origin of Clinical Strains of Sporothrix schenckii Complex in Mexico
J. Fungi 2018, 4(3), 86; https://doi.org/10.3390/jof4030086 (registering DOI)
Received: 14 June 2018 / Revised: 16 July 2018 / Accepted: 18 July 2018 / Published: 20 July 2018
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Abstract
Sporotrichosis is a subcutaneous mycosis caused by Sporothrix schenckii complex. The disease has been reported worldwide. However, the incidence of the etiological agent varies in its geographic distribution. We studied 39 clinical isolates of Sporothrix schenckii from diverse regions in Mexico, collected from
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Sporotrichosis is a subcutaneous mycosis caused by Sporothrix schenckii complex. The disease has been reported worldwide. However, the incidence of the etiological agent varies in its geographic distribution. We studied 39 clinical isolates of Sporothrix schenckii from diverse regions in Mexico, collected from 1998 to 2016. Molecular identification was performed by sequence analysis of the partial calmodulin gene. In vitro antifungal susceptibility to amphotericin B (AMB), itraconazole (ITC), voriconazole (VRC), posaconazole (PSC), fluconazole (FLC), terbinafine (TRB), caspofungin (CSF), anidulafungin (ANF), and micafungin (MCF) was evaluated. Thirty-eight isolates of S. schenckii complex were divided into five supported clades in a phylogenetic tree. The predominant clinical form was lymphocutaneous (92.3%), fixed cutaneous (5.1%), and disseminated (2.5%). Terbinafine exhibited the best in vitro antifungal activity, while fluconazole was ineffective against Sporothrix schenckii complex. Our results showed diverse geographic distribution of clinical isolates in eight states; definitive identification was done by CAL gen PCR-sequencing. In Mexico, S. schenckii is considered to be an etiological agent of human sporotrichosis cases, and lymphocutaneous is the most prevalent form of the disease. This study revealed four clades of S. schenckiisensu stricto by phylogenetic analysis. Furthermore, we report one case of S. globosa isolated from human origin from the North of Mexico. Full article
(This article belongs to the Special Issue Sporothrix and Sporotrichosis)
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Open AccessArticle PaPro1 and IDC4, Two Genes Controlling Stationary Phase, Sexual Development and Cell Degeneration in Podospora anserina
J. Fungi 2018, 4(3), 85; https://doi.org/10.3390/jof4030085
Received: 11 June 2018 / Revised: 28 June 2018 / Accepted: 10 July 2018 / Published: 11 July 2018
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Abstract
Filamentous fungi frequently undergo bistable phenotypic switches. Crippled Growth of Podospora anserina is one such bistable switch, which seems to rely upon the mis-activation of a self-regulated PaMpk1 MAP kinase regulatory pathway. Here, we identify two new partners of this pathway: PaPro1, a
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Filamentous fungi frequently undergo bistable phenotypic switches. Crippled Growth of Podospora anserina is one such bistable switch, which seems to rely upon the mis-activation of a self-regulated PaMpk1 MAP kinase regulatory pathway. Here, we identify two new partners of this pathway: PaPro1, a transcription factor orthologous to Sordaria macrospora pro1 and Neurospora crassa ADV-1, and IDC4, a protein with an AIM24 domain. Both PaPro1 and IDC4 regulate stationary phase features, as described for the other actors of the PaMpk1 signaling pathway. However, PaPro1 is also involved in the control of fertilization by activating the transcription of the HMG8 and the mating type transcription factors, as well as the sexual pheromones and receptor genes. The roles of two components of the STRIPAK complex were also investigated by inactivating their encoding genes: PaPro22 and PaPro45. The mutants of these genes were found to have the same phenotypes as PaPro1 and IDC4 mutants as well as additional phenotypes including slow growth, abnormally shaped hyphae, pigment accumulation and blockage of the zygotic tissue development, indicating that the STRIPAK complex regulates, in addition to the PaMpk1 one, other pathways in P. anserina. Overall, the mutants of these four genes confirm the model by which Crippled Growth is due to the abnormal activation of the PaMpk1 MAP kinase cascade. Full article
(This article belongs to the Special Issue Regulation of Fungal Morphogenesis and Gene Expression)
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Open AccessArticle Inter-Specimen Imbalance of Mitochondrial Gene Copy Numbers Predicts Clustering of Pneumocystis jirovecii Isolates in Distinct Subgroups
J. Fungi 2018, 4(3), 84; https://doi.org/10.3390/jof4030084
Received: 7 June 2018 / Revised: 4 July 2018 / Accepted: 9 July 2018 / Published: 10 July 2018
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Abstract
The molecular detection of Pneumocystis jirovecii is an important therapy-relevant tool in microbiological diagnostics. However, the quantification of this pathogen in the past has revealed discordant results depending on the target gene. As the clinical variety of P. jirovecii infections ranges between life-threatening
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The molecular detection of Pneumocystis jirovecii is an important therapy-relevant tool in microbiological diagnostics. However, the quantification of this pathogen in the past has revealed discordant results depending on the target gene. As the clinical variety of P. jirovecii infections ranges between life-threatening infections and symptom-free colonization, the question arises if qPCRs are reliable tools for quantitative diagnostics of P. jirovecii. P. jirovecii positive BALs were quantitatively tested for the copy numbers of one mitochondrial (COX-1) and two nuclear single-copy genes (KEX1 and DHPS) compared to the mitochondrial large subunit (mtLSU) by qPCR. Independent of the overall mtLSU copy number P. jirovecii clustered into distinct groups based on the ratio patterns of the respective qPCRs. This study, which compared different mitochondrial to nuclear gene ratio patterns of independent patients, shows that the mtLSU gene represents a highly sensitive qPCR tool for the detection of P. jirovecii, but does not display a reliable target for absolute quantification. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
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Open AccessReview Treatment of Infections Due to Aspergillus terreus Species Complex
J. Fungi 2018, 4(3), 83; https://doi.org/10.3390/jof4030083
Received: 14 June 2018 / Revised: 3 July 2018 / Accepted: 6 July 2018 / Published: 9 July 2018
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Abstract
The Aspergillus terreus species complex is found in a wide variety of habitats, and the spectrum of diseases caused covers allergic bronchopulmonary aspergillosis, Aspergillus bronchitis and/or tracheobronchitis, and invasive and disseminated aspergillosis. Invasive infections are a significant cause of morbidity and mortality mainly
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The Aspergillus terreus species complex is found in a wide variety of habitats, and the spectrum of diseases caused covers allergic bronchopulmonary aspergillosis, Aspergillus bronchitis and/or tracheobronchitis, and invasive and disseminated aspergillosis. Invasive infections are a significant cause of morbidity and mortality mainly in patients with hematological malignancy. The section Terrei covers a total of 16 accepted species of which most are amphotericin B resistant. Triazoles are the preferred agents for treatment and prevention of invasive aspergillosis. Poor prognosis in patients with invasive A. terreus infections seems to be independent of anti-Aspergillus azole-based treatment. Full article
(This article belongs to the Special Issue Treatments for Fungal Infections)
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Open AccessArticle Genotypic Diversity Is Independent of Pathogenicity in Colombian Strains of Cryptococcus neoformans and Cryptococcus gattii in Galleria mellonella
J. Fungi 2018, 4(3), 82; https://doi.org/10.3390/jof4030082
Received: 8 June 2018 / Revised: 29 June 2018 / Accepted: 30 June 2018 / Published: 5 July 2018
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Abstract
Cryptococcosis is a potentially fatal opportunistic mycosis that affects the lungs and central nervous system. It has been suggested that certain strains of C. neoformans/C. gattii may have the potential to be more virulent according to the molecular type. This study aims to
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Cryptococcosis is a potentially fatal opportunistic mycosis that affects the lungs and central nervous system. It has been suggested that certain strains of C. neoformans/C. gattii may have the potential to be more virulent according to the molecular type. This study aims to investigate the association between virulence in the G. mellonella model and genotypic diversity of Colombian clinical and environmental isolates of C. neoformans/C. gattii. A total of 33 clinical and 12 environmental isolates were selected according to their geographical origin and sequence types (STs). Pathogenicity was determined using the G. mellonella model, and the cell and capsular size before and after inoculation was determined. For C. neoformans, virulence in G. mellonella revealed that death occurred on average on day 6 (p < 0.05) and that ST5C, 6C, 25C and 71C were the most virulent. In C. gattii, death occurred at 7.3 days (p < 0.05), and ST47C, 58C, 75A and 106C were the most virulent. Capsular size increased for both species after passage in G. mellonella. In conclusion, the pathogenicity of Cryptococcus strains in the G. mellonella invertebrate model is independent of molecular type or pathogenicity factor, even within the same ST, but it is possible to find variable degrees of pathogenicity. Full article
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Open AccessReview Identification of Antifungal Targets Based on Computer Modeling
J. Fungi 2018, 4(3), 81; https://doi.org/10.3390/jof4030081
Received: 15 May 2018 / Revised: 24 June 2018 / Accepted: 29 June 2018 / Published: 4 July 2018
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Abstract
Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to
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Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host–pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools. Full article
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Open AccessEditorial Special Issue “Fungal Burden in Different Countries”
J. Fungi 2018, 4(3), 80; https://doi.org/10.3390/jof4030080
Received: 29 June 2018 / Revised: 2 July 2018 / Accepted: 2 July 2018 / Published: 3 July 2018
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Abstract
Adults and children living in many countries face a combined burden of infectious diseases
including fungal infections (for example, tinea capitis, recurrent vulvo-vaginal thrush, chronic
pulmonary aspergillosis, candidemia) [...] Full article
(This article belongs to the Special Issue Fungal Burden in Different Countries)
Open AccessReview Present and Future Therapy of Cryptococcus Infections
J. Fungi 2018, 4(3), 79; https://doi.org/10.3390/jof4030079
Received: 19 May 2018 / Revised: 25 June 2018 / Accepted: 26 June 2018 / Published: 3 July 2018
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Abstract
Cryptococcal infections burden the immunocompromised population with unacceptably high morbidity and mortality. This population includes HIV-infected individuals and those undergoing organ transplants, as well as seemingly immunocompetent patients (non-HIV, non-transplant). These groups are difficult to manage with the current therapeutic options and strategies,
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Cryptococcal infections burden the immunocompromised population with unacceptably high morbidity and mortality. This population includes HIV-infected individuals and those undergoing organ transplants, as well as seemingly immunocompetent patients (non-HIV, non-transplant). These groups are difficult to manage with the current therapeutic options and strategies, particularly in resource-limited settings. New trials aimed at providing the best treatment strategies for resource-limited countries that will reduce costs and adverse reactions have focused on decreasing the length of therapy and using more readily accessible antifungal agents such as fluconazole. Furthermore, the emergence of antifungal resistance poses another challenge for successful treatment and may require the development of new agents for improved management. This review will discuss the principles of management, current and future antifungal agents, as well as emerging techniques and future directions of care for this deadly infection. Full article
(This article belongs to the Special Issue Treatments for Fungal Infections)
Open AccessArticle Biological Roles of Protein-Coding Tandem Repeats in the Yeast Candida Albicans
J. Fungi 2018, 4(3), 78; https://doi.org/10.3390/jof4030078
Received: 23 May 2018 / Revised: 16 June 2018 / Accepted: 27 June 2018 / Published: 29 June 2018
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Abstract
Tandem repeat (TR) DNA mutates faster than other DNA by insertion and deletion of repeats. Large parts of eukaryotic proteomes are encoded by ORFs containing protein-coding TRs (TR-ORFs, pcTRs) with largely unknown biological consequences. We explored these in the yeast Candida albicans,
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Tandem repeat (TR) DNA mutates faster than other DNA by insertion and deletion of repeats. Large parts of eukaryotic proteomes are encoded by ORFs containing protein-coding TRs (TR-ORFs, pcTRs) with largely unknown biological consequences. We explored these in the yeast Candida albicans, an opportunistic human pathogen. We found that almost half of C. albicans’ proteins are encoded by TR-ORFs. pcTR frequency differed only moderately between different gene (GO) categories. Bioinformatic predictions of genome-wide mutation rates and clade-specific differences in pcTR allele frequencies indicated that pcTRs (i) significantly increase the genome-wide mutation rate; (ii) significantly impact on fitness and (iii) allow the evolution of selectively advantageous clade-specific protein variants. Synonymous mutations reduced the repetitiveness of many amino acid repeat-encoding pcTRs. A survey, in 58 strains, revealed that in some pcTR regions in which repetitiveness was not significantly diminished by synonymous mutations the habitat predicted which alleles were present, suggesting roles of pcTR mutation in short-term adaptation and pathogenesis. In C. albicans pcTR mutation apparently is an important mechanism for mutational advance and possibly also rapid adaptation, with synonymous mutations providing a mechanism for adjusting mutation rates of individual pcTRs. Analyses of Arabidopsis and human pcTRs showed that the latter also occurs in other eukaryotes. Full article
(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)
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Open AccessReview Endophytic Fungi: A Source of Potential Antifungal Compounds
J. Fungi 2018, 4(3), 77; https://doi.org/10.3390/jof4030077
Received: 20 May 2018 / Revised: 13 June 2018 / Accepted: 16 June 2018 / Published: 25 June 2018
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Abstract
The emerging and reemerging forms of fungal infections encountered in the course of allogeneic bone marrow transplantations, cancer therapy, and organ transplants have necessitated the discovery of antifungal compounds with enhanced efficacy and better compatibility. A very limited number of antifungal compounds are
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The emerging and reemerging forms of fungal infections encountered in the course of allogeneic bone marrow transplantations, cancer therapy, and organ transplants have necessitated the discovery of antifungal compounds with enhanced efficacy and better compatibility. A very limited number of antifungal compounds are in practice against the various forms of topical and systemic fungal infections. The trends of new antifungals being introduced into the market have remained insignificant while resistance towards the introduced drug has apparently increased, specifically in patients undergoing long-term treatment. Considering the immense potential of natural microbial products for the isolation and screening of novel antibiotics for different pharmaceutical applications as an alternative source has remained largely unexplored. Endophytes are one such microbial community that resides inside all plants without showing any symptoms with the promise of producing diverse bioactive molecules and novel metabolites which have application in medicine, agriculture, and industrial set ups. This review substantially covers the antifungal compounds, including volatile organic compounds, isolated from fungal endophytes of medicinal plants during 2013–2018. Some of the methods for the activation of silent biosynthetic genes are also covered. As such, the compounds described here possess diverse configurations which can be a step towards the development of new antifungal agents directly or precursor molecules after the required modification. Full article
(This article belongs to the Special Issue Fungal Endophytes in Plants)
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Open AccessArticle Estimated Burden of Serious Fungal Diseases in Serbia
J. Fungi 2018, 4(3), 76; https://doi.org/10.3390/jof4030076
Received: 25 May 2018 / Revised: 18 June 2018 / Accepted: 19 June 2018 / Published: 25 June 2018
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Abstract
For the first time, we aimed to estimate the burden of serious fungal infections or diseases (SFD) and highlight national epidemiological features in Serbia. Data on population and underlining conditions were extracted from the Statistical Office of the Republic of Serbia, World Bank,
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For the first time, we aimed to estimate the burden of serious fungal infections or diseases (SFD) and highlight national epidemiological features in Serbia. Data on population and underlining conditions were extracted from the Statistical Office of the Republic of Serbia, World Bank, the Institute of Public Health of Serbia, the World Health Organization, National reference laboratory for medical mycology, the national registries of Serbian professional societies, and relevant publications. The population structure/inhabitants in 2016 (not including the autonomous region Kosovo & Metohija) was 7,058,322; with 6,041,743 adults (85.6%). The populations at risk (total cases per year) were: HIV infected 2441; acute myeloid leukemia 212; stem cell transplantation 151; solid organ transplants 59; chronic obstructive pulmonary disease 250,302; adult asthmatics 311,806; adult cystic fibrosis 65; pulmonary tuberculosis 898; lung cancer 7260; intensive care unit admissions 19,821; and renal support 520. Annual fungal disease cases estimated are: candidemia 518; invasive aspergillosis 619; Candida peritonitis 187; Pneumocystis jirovecii pneumonia 62; cryptococcosis 5; mucormycosis or fusariosis 23; severe asthma with fungal sensitization 10,393; allergic bronchopulmonary aspergillosis 9094; chronic pulmonary aspergillosis 448, recurrent Candida vaginitis 135,303; oral candidiasis 208,489; esophageal candidiasis 173, fungal keratitis 70; tinea capitis 300; and onychomycosis 342,721. We expect that 156,825 people suffer from serious SFD each year (2221/100,000), and 409 dies annually. Additionally, the prevalence of superficial infections exceeds 1,008,995 cases (14,295/100,000). The first Rhinosporidium outbreak in Europe was associated with Serbian Silver Lake. The plant pathogen Fusarium seems to be emerging in Serbian pediatric haematooncology settings. Candida auris and endemic mycoses have not been observed to date. These general estimates provide a primer for further efforts to study fungal epidemiology in Serbia. Full article
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Open AccessArticle Estimated Burden of Serious Fungal Infections in Mozambique
J. Fungi 2018, 4(3), 75; https://doi.org/10.3390/jof4030075
Received: 6 June 2018 / Revised: 22 June 2018 / Accepted: 22 June 2018 / Published: 23 June 2018
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Abstract
Mozambique is a sub-Saharan African country with limited information on the burden of fungal disease. We estimated the burden of serious fungal infections for the general healthy population and for those at risk, including those infected with HIV, patients with asthma, as well
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Mozambique is a sub-Saharan African country with limited information on the burden of fungal disease. We estimated the burden of serious fungal infections for the general healthy population and for those at risk, including those infected with HIV, patients with asthma, as well as those under intensive care. We consulted the Mozambican National Institute of Statistics Population and Housing Census report to obtain denominators for different age groups. We use modelling and HIV data to estimate the burdens of Pneumocystis jirovecii pneumonia (PCP), cryptococcal meningitis (CM) and candidiasis. Asthma, chronic obstructive pulmonary disease and tuberculosis data were used to estimate the burden of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). In 2016, the Mozambique population was 26.4 million with 1.8 million people reported to be HIV-infected. Estimated annual incidence of fungal infections was: 33,380 PCP, 18,640 CM and 260,025 oral and oesophageal candidiasis cases. Following pulmonary tuberculosis, estimated numbers of people having chronic pulmonary aspergillosis (prevalence) and allergic bronchopulmonary aspergillosis complicating asthma are 18,475 and 15,626, respectively. Tinea capitis is common in children with over 1.1 million probably affected. We also highlight from studies in progress of high incidences of histoplasmosis, CM and Pneumocystis jirovecii in adult HIV-infected patients. Prospective epidemiology studies with sensitive diagnostics are required to validate these estimates. Full article
(This article belongs to the Special Issue Fungal Burden in Different Countries)
Open AccessEditorial Special Issue: Candida and Candidiasis
J. Fungi 2018, 4(3), 74; https://doi.org/10.3390/jof4030074
Received: 19 June 2018 / Revised: 19 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
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Abstract
This special issue highlights emerging topics related to Candida, the most prevalent fungal pathogen in the hospital setting. The advantages and limitations of new, non-culture based diagnostic techniques are discussed. The issue reviews mammalian and non-mammalian infection models. The manuscripts present updates
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This special issue highlights emerging topics related to Candida, the most prevalent fungal pathogen in the hospital setting. The advantages and limitations of new, non-culture based diagnostic techniques are discussed. The issue reviews mammalian and non-mammalian infection models. The manuscripts present updates on several molecular mechanisms of pathogenicity, including filamentation, biofilm formation, and phospholipid production. Full article
(This article belongs to the Special Issue Candida and Candidiasis)
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