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Microorganisms
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Advances in Cryptococcus and Cryptococcosis
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Advances in 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 May 2022) | Viewed by 9480

Special Issue Editors

Dr. Nuria Trevijano-Contador

E-Mail Website
Guest Editor
Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, 28222 Madrid, Spain
Interests: Cryptococcus neoformans; antibodies; host-pathogen interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Haroldo Cesar de Oliveira

E-Mail Website
Guest Editor
Carlos Chagas Institute, Fiocruz, Curitiba, Brazil
Interests: anticryptococcal drugs; vesicles of C. neoformans

Special Issue Information

Dear Colleagues,

Cryptococcosis is a fungal disease that claims more than 180,000 victims annually and is caused by the environmental fungi C. neoformans and C. gattii. These species are known for their ability to adapt to the host environment and migrate to the central nervous system, causing the most severe form of the disease, the cryptococcal meningitis, a lethal complication that is still a major therapeutic challenge. Different aspects of this yeast, i.e., virulence factors, interaction with host cells, alternative therapies, among others, have been explored by researchers with different advances in methodologies in the last few years. In 2018, several groups described an in vitro method to induce Titan cell formation, overcoming the challenge of working with animal models to obtain them, bringing important advances in the knowledge of the biology of these cells. Following this example, we invite researchers to share with us new advances, methodologies and knowledge on Cryptococcus and cryptococcosis with research papers, in addition to literature revisions, that compile recent advances in the knowledge of the biology of C. neoformans and C. gattii

Dr. Nuria Trevijano-Contador
Dr. Haroldo Cesar de Oliveira
Guest Editors

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

  • C. neoformans
  • C. gattii
  • in vitro methods
  • virulence factors
  • host
  • capsule
  • titan cells
  • anti-cryptococcal agents
  • host immune response to cryptococcosis
  • therapies

Related Special Issue

Published Papers (5 papers)

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Research

7 pages, 658 KiB  
Communication
Phylogenomic Placement of American Southwest-Associated Clinical and Veterinary Isolates Expands Evidence for Distinct Cryptococcus gattii VGVI
by Juan Monroy-Nieto, Jolene R. Bowers, Parker Montfort, Guillermo Adame, Constanza Giselle Taverna, Hayley Yaglom, Jane E. Sykes, Shane Brady, A. Brian Mochon, Wieland Meyer, Kenneth Komatsu and David M. Engelthaler
Microorganisms 2022, 10(8), 1681; https://doi.org/10.3390/microorganisms10081681 - 20 Aug 2022
Cited by 4 | Viewed by 1708
Abstract
Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the [...] Read more.
Whole-genome sequencing has advanced our understanding of the population structure of the pathogenic species complex Cryptococcus gattii, which has allowed for the phylogenomic specification of previously described major molecular type groupings and novel lineages. Recently, isolates collected in Mexico in the 1960s were determined to be genetically distant from other known molecular types and were classified as VGVI. We sequenced four clinical isolates and one veterinary isolate collected in the southwestern United States and Argentina from 2012 to 2021. Phylogenomic analysis groups these genomes with those of the Mexican VGVI isolates, expanding VGVI into a clade and establishing this molecular type as a clinically important population. These findings also potentially expand the known Cryptococcus ecological range with a previously unrecognized endemic area. Full article
(This article belongs to the Special Issue Advances in Cryptococcus and Cryptococcosis)
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11 pages, 657 KiB  
Article
Cryptococcosis: Identification of Risk Areas in the Brazilian Amazon
by Danielle Saraiva Tuma dos Reis, Mioni Thieli Figueiredo Magalhães de Brito, Ricardo José de Paula Souza Guimarães and Juarez Antônio Simões Quaresma
Microorganisms 2022, 10(7), 1411; https://doi.org/10.3390/microorganisms10071411 - 13 Jul 2022
Viewed by 1259
Abstract
The Brazilian Amazon has a specific epidemiological profile for cryptococcosis, considering its social and economic inequality, health reality, and low access to health services. Furthermore, Brazil and Colombia have the highest cryptococcosis incidence rates in Latin America. In this study, we identified the [...] Read more.
The Brazilian Amazon has a specific epidemiological profile for cryptococcosis, considering its social and economic inequality, health reality, and low access to health services. Furthermore, Brazil and Colombia have the highest cryptococcosis incidence rates in Latin America. In this study, we identified the areas of risk for cryptococcosis in the state of Pará in the Brazilian Amazon. This was an ecological study of patients admitted to a referral hospital from 2008 to 2018, aged 13 years or older, and of both sexes. The spatial distribution was determined using ArcGis 10.3.1 software. Cryptococcosis was confirmed in 272 cases. The incidence rate was 3.41 cases/100,000 inhabitants. Spatial distribution was concentrated in the Metropolitana de Belém, Nordeste Paraense, and Marajó mesoregions. The sociodemographic profile consisted of 62% men, aged between 24 and 34 years (36%), without completed secondary education (64.7%), and with occupations varying between agricultural activities (13.8%) and household activities (22%). The mean hospitalization time was 39 days; the prevalent clinical form was neurological (89.7%). The mortality rate among patients with cryptococcosis was up to 40%. Knowledge of the real magnitude of the disease in the Brazilian Amazon makes it possible to identify areas with the greatest risks and to propose control and epidemiological surveillance programs. Full article
(This article belongs to the Special Issue Advances in Cryptococcus and Cryptococcosis)
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9 pages, 665 KiB  
Article
Epidemiology and Mortality of Cryptococcal Disease in Guatemala: Two-Year Results of a Cryptococcal Antigen Screening Program
by Narda Medina, Juan Luis Rodriguez-Tudela, Juan Carlos Pérez, Danicela Mercado, Oscar Bonilla, Eduardo Arathoon and Ana Alastruey-Izquierdo
Microorganisms 2022, 10(7), 1388; https://doi.org/10.3390/microorganisms10071388 - 10 Jul 2022
Cited by 3 | Viewed by 1560
Abstract
Cryptococcal disease is an important opportunistic infection among people living with HIV. The cryptococcal antigen (CrAg) can be detected before the clinical onset of meningitis and its screening is recommended. Here, we evaluated CrAg frequency, and describe the epidemiological characteristics and mortality at [...] Read more.
Cryptococcal disease is an important opportunistic infection among people living with HIV. The cryptococcal antigen (CrAg) can be detected before the clinical onset of meningitis and its screening is recommended. Here, we evaluated CrAg frequency, and describe the epidemiological characteristics and mortality at 180 days in a cohort of HIV patients from Guatemala. A total of 3457 patients were screened with a CrAg lateral flow assay in serum between January 2017 and December 2018. CrAg positivity was 11.5% in patients with ≤100 CD4/mm3, 8.7% in patients with <200 CD4/mm3, and 6.3% in patients with <350 CD4/mm3. In Latin America, we estimated 9.2% CrAg positivity (IC95% 7.9–10.7%) in patients with ≤100 CD4/mm3. Among patients newly diagnosed with HIV, we estimated 4416 incident cases per year in Latin America in those with <200 CD4/mm3 and 5289 in those with <350 CD4/mm3. In addition, we calculated the burden in people not on ARV or without viral suppression and found 28,672 cases. CrAg screening should be considered in patients who have a CD4 cell count < 350 cells/mm3. Cryptococcal meningitis was associated with 30.8% mortality in Guatemala. Global access to diagnosis as well as to liposomal amphotericin B and flucytosine is a priority. Full article
(This article belongs to the Special Issue Advances in Cryptococcus and Cryptococcosis)
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14 pages, 2768 KiB  
Article
Role of IL-17 in Morphogenesis and Dissemination of Cryptococcus neoformans during Murine Infection
by Nuria Trevijano-Contador, Elena Roselletti, Rocío García-Rodas, Anna Vecchiarelli and Óscar Zaragoza
Microorganisms 2022, 10(2), 373; https://doi.org/10.3390/microorganisms10020373 - 05 Feb 2022
Cited by 1 | Viewed by 1663
Abstract
Cryptococcus neoformans is a pathogenic yeast that can form Titan cells in the lungs, which are fungal cells of abnormally large size. The factors that regulate Titan cell formation in vivo are still unknown, although an increased proportion of these fungal cells of [...] Read more.
Cryptococcus neoformans is a pathogenic yeast that can form Titan cells in the lungs, which are fungal cells of abnormally large size. The factors that regulate Titan cell formation in vivo are still unknown, although an increased proportion of these fungal cells of infected mice correlates with induction of Th2-type responses. Here, we focused on the role played by the cytokine IL-17 in the formation of cryptococcal Titan cells using Il17a−/− knockout mice. We found that after 9 days of infection, there was a lower proportion of Titan cells in Il17a−/− mice compared to the fungal cells found in wild-type animals. Dissemination to the brain occurred earlier in Il17a−/− mice, which correlated with the lower proportion of Titan cells in the lungs. Furthermore, knockout-infected mice increased brain size more than WT mice. We also determined the profile of cytokines accumulated in the brain, and we found significant differences between both mouse strains. We found that in Il17a−/−, there was a modest increase in the concentrations of the Th1 cytokine TNF-α. To validate if the increase in this cytokine had any role in cryptococcal morphogenesis, we injected wild-type mice with TNF-α t and observed that fungal cell size was significantly reduced in mice treated with this cytokine. Our results suggest a compensatory production of cytokines in Il17a−/− mice that influences both cryptococcal morphology and dissemination. Full article
(This article belongs to the Special Issue Advances in Cryptococcus and Cryptococcosis)
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17 pages, 4230 KiB  
Article
Genetic and Phenotypic Diversities in Experimental Populations of Diploid Inter-Lineage Hybrids in the Human Pathogenic Cryptococcus
by Man You, Yuxin Monica Lin, Annamaria Dobrin and Jianping Xu
Microorganisms 2021, 9(8), 1579; https://doi.org/10.3390/microorganisms9081579 - 24 Jul 2021
Cited by 2 | Viewed by 2295
Abstract
To better understand the potential factors contributing to genome instability and phenotypic diversity, we conducted mutation accumulation (MA) experiments for 120 days for 7 diploid cryptococcal hybrids under fluconazole (10 MA lines each) and non-fluconazole conditions (10 MA lines each). The genomic DNA [...] Read more.
To better understand the potential factors contributing to genome instability and phenotypic diversity, we conducted mutation accumulation (MA) experiments for 120 days for 7 diploid cryptococcal hybrids under fluconazole (10 MA lines each) and non-fluconazole conditions (10 MA lines each). The genomic DNA content, loss of heterozygosity (LOH) rate, growth ability, and fluconazole susceptibility were determined for all 140 evolved cultures. Compared to that of their ancestral clones, the evolved clones showed: (i) genomic DNA content changes ranging from ~22% less to ~27% more, and (ii) reduced, similar, and increased phenotypic values for each tested trait, with most evolved clones displaying increased growth at 40 °C and increased fluconazole resistance. Aside from the ancestral multi-locus genotypes (MLGs) and heterozygosity patterns (MHPs), 77 unique MLGs and 70 unique MPHs were identified among the 140 evolved cultures at day 120. The average LOH rates of the MA lines in the absence and presence of fluconazole were similar at 1.27 × 10−4 and 1.38 × 10−4 LOH events per MA line per mitotic division, respectively. While LOH rates varied among MA lines from different ancestors, there was no apparent correlation between the genetic divergence of the parental haploid genomes within ancestral clones and LOH rates. Together, our results suggest that hybrids between diverse lineages of the human pathogenic Cryptococcus can generate significant genotypic and phenotypic diversities during asexual reproduction. Full article
(This article belongs to the Special Issue Advances in Cryptococcus and Cryptococcosis)
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