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Microorganisms
Special Issues
Current Understanding of Cryptococcus and Cryptococcosis
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Current Understanding of Cryptococcus and Cryptococcosis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 19045

Special Issue Editor

Dr. Simon Johnston

E-Mail Website
Guest Editor
Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, South Yorkshire, UK
Interests: fungal infections; mmunocompromise; Cryptococcus

Special Issue Information

Dear Colleagues,

Cryptococcus is a genus of basidiomycete yeast and a highly successful fungal pathogen in animals that causes cryptococcosis. In humans, cryptococcal infection is most commonly associated with severe immunocompromise, and is the cause of hundreds of thousands of deaths and an estimated 15% of acquired immune deficiency syndrome (AIDS)-related deaths. Life-threatening infection most often takes the form of meningitis, which results from the dissemination of pulmonary infection. A number of species cause infection, with Cryptococcus neoformans the major pathogenic species. Infection with Cryptococcus gattii is unusual, as it can occur in the immunocompetent and is the cause of an ongoing outbreak in North America that originated in Vancouver Island, Canada.

This Special Issue aims to present the diversity and complexity of Cryptococcus and cryptococcosis, from molecular microbiology to clinical studies. The study of Cryptococcus has generated key findings in a wide range of fields. We embrace the diversity of Cryptococcus and cryptococcosis research and welcome any submissions related to the study of this intriguing yeast and pathogen.

Figure 1. Fluorescent labeling of Cryptococcus neoformans Image. Credit: Ffion Hammond, University of Sheffield.

Dr. Simon Johnston
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cryptococcus
  • cryptococcosis
  • cryptococcal meningitis
  • fungal biology
  • fungal genetics
  • host–pathogen interactions
  • fungal immunology
  • medical mycology

Published Papers (5 papers)

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Research

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17 pages, 2251 KiB  
Article
Nutritional Conditions Modulate C. neoformans Extracellular Vesicles’ Capacity to Elicit Host Immune Response
by Clara Luna Marina, Pedro Henrique Bürgel, Daniel Paiva Agostinho, Daniel Zamith-Miranda, Lucas de Oliveira Las-Casas, Aldo Henrique Tavares, Joshua Daniel Nosanchuk and Anamelia Lorenzetti Bocca
Microorganisms 2020, 8(11), 1815; https://doi.org/10.3390/microorganisms8111815 - 18 Nov 2020
Cited by 14 | Viewed by 2410
Abstract
Cryptococcus neoformans is a human pathogenic fungus that mainly afflicts immunocompromised patients. One of its virulence strategies is the production of extracellular vesicles (EVs), containing cargo with immunomodulatory properties. We evaluated EV’s characteristics produced by capsular and acapsular strains of C. neoformans (B3501 [...] Read more.
Cryptococcus neoformans is a human pathogenic fungus that mainly afflicts immunocompromised patients. One of its virulence strategies is the production of extracellular vesicles (EVs), containing cargo with immunomodulatory properties. We evaluated EV’s characteristics produced by capsular and acapsular strains of C. neoformans (B3501 and ΔCap67, respectively) growing in nutritionally poor or rich media and co-cultures with bone marrow-derived macrophages or dendritic cells from C57BL/6 mice. EVs produced under a poor nutritional condition displayed a larger hydrodynamic size, contained more virulence compounds, and induced a more robust inflammatory pattern than those produced in a rich nutritional medium, independently of strain. We treated infected mice with EVs produced in the rich medium, and the EVs inhibited more genes related to the inflammasome than untreated infected mice. These findings suggest that the EVs participate in the pathogenic processes that result in the dissemination of C. neoformans. Thus, these results highlight the versatility of EVs’ properties during infection by C. neoformans in different tissues and support ongoing efforts to harness EVs to prevent and treat cryptococcosis. Full article
(This article belongs to the Special Issue Current Understanding of Cryptococcus and Cryptococcosis)
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20 pages, 9422 KiB  
Article
The Role of Oxidoreductase-Like Protein Olp1 in Sexual Reproduction and Virulence of Cryptococcus neoformans
by Qi-Kun Yu, Lian-Tao Han, Yu-Juan Wu and Tong-Bao Liu
Microorganisms 2020, 8(11), 1730; https://doi.org/10.3390/microorganisms8111730 - 04 Nov 2020
Cited by 6 | Viewed by 2365
Abstract
Cryptococcus neoformans is a basidiomycete human fungal pathogen causing lethal meningoencephalitis, mainly in immunocompromised patients. Oxidoreductases are a class of enzymes that catalyze redox, playing a crucial role in biochemical reactions. In this study, we identified one Cryptococcus oxidoreductase-like protein-encoding gene OLP1 and [...] Read more.
Cryptococcus neoformans is a basidiomycete human fungal pathogen causing lethal meningoencephalitis, mainly in immunocompromised patients. Oxidoreductases are a class of enzymes that catalyze redox, playing a crucial role in biochemical reactions. In this study, we identified one Cryptococcus oxidoreductase-like protein-encoding gene OLP1 and investigated its role in the sexual reproduction and virulence of C. neoformans. Gene expression patterns analysis showed that the OLP1 gene was expressed in each developmental stage of Cryptococcus, and the Olp1 protein was located in the cytoplasm of Cryptococcus cells. Although it produced normal major virulence factors such as melanin and capsule, the olp1Δ mutants showed growth defects on the yeast extract peptone dextrose (YPD) medium supplemented with lithium chloride (LiCl) and 5-fluorocytosine (5-FC). The fungal mating analysis showed that Olp1 is also essential for fungal sexual reproduction, as olp1Δ mutants show significant defects in hyphae growth and basidiospores production during bisexual reproduction. The fungal nuclei imaging showed that during the bilateral mating of olp1Δ mutants, the nuclei failed to undergo meiosis after fusion in the basidia, indicating that Olp1 is crucial for regulating meiosis during mating. Moreover, Olp1 was also found to be required for fungal virulence in C. neoformans, as the olp1Δ mutants showed significant virulence attenuation in a murine inhalation model. In conclusion, our results showed that the oxidoreductase-like protein Olp1 is required for both fungal sexual reproduction and virulence in C. neoformans. Full article
(This article belongs to the Special Issue Current Understanding of Cryptococcus and Cryptococcosis)
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10 pages, 1400 KiB  
Article
Indoor Dust as a Source of Virulent Strains of the Agents of Cryptococcosis in the Rio Negro Micro-Region of the Brazilian Amazon
by Fábio Brito-Santos, Luciana Trilles, Carolina Firacative, Bodo Wanke, Filipe Anibal Carvalho-Costa, Marília Martins Nishikawa, Jonas Pereira Campos, Angela Cristina Veríssimo Junqueira, Amanda Coutinho de Souza, Márcia dos Santos Lazéra and Wieland Meyer
Microorganisms 2020, 8(5), 682; https://doi.org/10.3390/microorganisms8050682 - 07 May 2020
Cited by 9 | Viewed by 2298
Abstract
Cryptococcosis, a potentially fatal mycosis in humans, is acquired via exposure to exogenous environmental sources. This study aimed to investigate the frequency, genetic diversity, and virulence of cryptococcal strains isolated from indoor dust in the Rio Negro micro-region of the Brazilian Amazon. A [...] Read more.
Cryptococcosis, a potentially fatal mycosis in humans, is acquired via exposure to exogenous environmental sources. This study aimed to investigate the frequency, genetic diversity, and virulence of cryptococcal strains isolated from indoor dust in the Rio Negro micro-region of the Brazilian Amazon. A total of 8.9% of the studied houses were positive, recovering nine Cryptococcus neoformans VNI and 16 C. gattii VGII isolates, revealing an endemic pattern in domestic microenvironments. The International Society for Human and Animal Mycology (ISHAM) consensus multilocus sequence typing (MLST) scheme for the C. neoformans/C. gattii species complexes identified two sequence types (STs), ST93 and ST5, amongst C. neoformans isolates and six STs amongst C. gattii isolates, including the Vancouver Island Outbreak ST7 (VGIIa) and ST20 (VGIIb), the Australian ST5, and ST264, ST268 and ST445, being unique to the studied region. Virulence studies in the Galleria mellonella model showed that five C. gattii strains and one C. neoformans strain showed a similar pathogenic potential to the highly virulent Vancouver Island outbreak strain CDR265 (VGIIa). The findings of this study indicate that humans can be exposed to the agents of cryptococcosis via house dust, forming the basis for future studies to analyze the impact of early and continuous exposure to indoor dust on the development of subclinical or clinical infections. Full article
(This article belongs to the Special Issue Current Understanding of Cryptococcus and Cryptococcosis)
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Review

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15 pages, 3795 KiB  
Review
New Approaches for Cryptococcosis Treatment
by Cristina de Castro Spadari, Fernanda Wirth, Luciana Biagini Lopes and Kelly Ishida
Microorganisms 2020, 8(4), 613; https://doi.org/10.3390/microorganisms8040613 - 23 Apr 2020
Cited by 43 | Viewed by 6931
Abstract
Cryptococcosis is an important opportunistic infection and a leading cause of meningitis in patients with HIV infection. The antifungal pharmacological treatment is limited to amphotericin B, fluconazole and 5- flucytosine. In addition to the limited pharmacological options, the high toxicity, increased resistance rate [...] Read more.
Cryptococcosis is an important opportunistic infection and a leading cause of meningitis in patients with HIV infection. The antifungal pharmacological treatment is limited to amphotericin B, fluconazole and 5- flucytosine. In addition to the limited pharmacological options, the high toxicity, increased resistance rate and difficulty of the currently available antifungal molecules to cross the blood–brain barrier hamper the treatment. Thus, the search for new alternatives for the treatment of cryptococcal meningitis is extremely necessary. In this review, we describe the therapeutic strategies currently available, discuss new molecules with antifungal potential in different phases of clinical trials and in advanced pre-clinical phase, and examine drug nanocarriers to improve delivery to the central nervous system. Full article
(This article belongs to the Special Issue Current Understanding of Cryptococcus and Cryptococcosis)
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19 pages, 809 KiB  
Review
Environmental Factors That Contribute to the Maintenance of Cryptococcus neoformans Pathogenesis
by Maphori Maliehe, Mathope A. Ntoi, Shayanki Lahiri, Olufemi S. Folorunso, Adepemi O. Ogundeji, Carolina H. Pohl and Olihile M. Sebolai
Microorganisms 2020, 8(2), 180; https://doi.org/10.3390/microorganisms8020180 - 28 Jan 2020
Cited by 16 | Viewed by 4283
Abstract
The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host–pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of [...] Read more.
The ability of microorganisms to colonise and display an intracellular lifestyle within a host body increases their fitness to survive and avoid extinction. This host–pathogen association drives microbial evolution, as such organisms are under selective pressure and can become more pathogenic. Some of these microorganisms can quickly spread through the environment via transmission. The non-transmittable fungal pathogens, such as Cryptococcus, probably return into the environment upon decomposition of the infected host. This review analyses whether re-entry of the pathogen into the environment causes restoration of its non-pathogenic state or whether environmental factors and parameters assist them in maintaining pathogenesis. Cryptococcus (C.) neoformans is therefore used as a model organism to evaluate the impact of environmental stress factors that aid the survival and pathogenesis of C. neoformans intracellularly and extracellularly. Full article
(This article belongs to the Special Issue Current Understanding of Cryptococcus and Cryptococcosis)
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