Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
PLoS Biol ; 21(5): e3001822, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37205709

RESUMO

Candida albicans is a frequent colonizer of human mucosal surfaces as well as an opportunistic pathogen. C. albicans is remarkably versatile in its ability to colonize diverse host sites with differences in oxygen and nutrient availability, pH, immune responses, and resident microbes, among other cues. It is unclear how the genetic background of a commensal colonizing population can influence the shift to pathogenicity. Therefore, we examined 910 commensal isolates from 35 healthy donors to identify host niche-specific adaptations. We demonstrate that healthy people are reservoirs for genotypically and phenotypically diverse C. albicans strains. Using limited diversity exploitation, we identified a single nucleotide change in the uncharacterized ZMS1 transcription factor that was sufficient to drive hyper invasion into agar. We found that SC5314 was significantly different from the majority of both commensal and bloodstream isolates in its ability to induce host cell death. However, our commensal strains retained the capacity to cause disease in the Galleria model of systemic infection, including outcompeting the SC5314 reference strain during systemic competition assays. This study provides a global view of commensal strain variation and within-host strain diversity of C. albicans and suggests that selection for commensalism in humans does not result in a fitness cost for invasive disease.


Assuntos
Candida albicans , Simbiose , Humanos , Candida albicans/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica
2.
Proc Natl Acad Sci U S A ; 119(36): e2116841119, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36037379

RESUMO

Most of the described species in kingdom Fungi are contained in two phyla, the Ascomycota and the Basidiomycota (subkingdom Dikarya). As a result, our understanding of the biology of the kingdom is heavily influenced by traits observed in Dikarya, such as aerial spore dispersal and life cycles dominated by mitosis of haploid nuclei. We now appreciate that Fungi comprises numerous phylum-level lineages in addition to those of Dikarya, but the phylogeny and genetic characteristics of most of these lineages are poorly understood due to limited genome sampling. Here, we addressed major evolutionary trends in the non-Dikarya fungi by phylogenomic analysis of 69 newly generated draft genome sequences of the zoosporic (flagellated) lineages of true fungi. Our phylogeny indicated five lineages of zoosporic fungi and placed Blastocladiomycota, which has an alternation of haploid and diploid generations, as branching closer to the Dikarya than to the Chytridiomyceta. Our estimates of heterozygosity based on genome sequence data indicate that the zoosporic lineages plus the Zoopagomycota are frequently characterized by diploid-dominant life cycles. We mapped additional traits, such as ancestral cell-cycle regulators, cell-membrane- and cell-wall-associated genes, and the use of the amino acid selenocysteine on the phylogeny and found that these ancestral traits that are shared with Metazoa have been subject to extensive parallel loss across zoosporic lineages. Together, our results indicate a gradual transition in the genetics and cell biology of fungi from their ancestor and caution against assuming that traits measured in Dikarya are typical of other fungal lineages.


Assuntos
Fungos , Estágios do Ciclo de Vida , Filogenia , Diploide , Fungos/classificação , Fungos/genética , Genoma Fúngico/genética
3.
Immunogenetics ; 74(4): 431-441, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35080658

RESUMO

Habitat fragmentation and infectious diseases threaten wildlife globally, but the interactions of these threats are poorly understood. For instance, while habitat fragmentation can impact genetic diversity at neutral loci, the impacts on disease-relevant loci are less well-studied. We examined the effects of habitat fragmentation in Brazil's Atlantic Forest on amphibian genetic diversity at an immune locus related to antigen presentation and detection (MHC IIB Exon 2). We used a custom high-throughput assay to sequence a fragment of MHC IIB and quantified Batrachochytrium dendrobatidis (Bd) infections in six frog species in two Atlantic Forest regions. Habitat fragmentation was associated with genetic erosion at MHC IIB Exon 2. This erosion was most severe in forest specialists. Significant Bd infections were detected only in one Atlantic Forest region, potentially due to relatively higher elevation. In this region, forest specialists showed an increase in both Bd prevalence and infection loads in fragmented habitats. Reduced population-level MHC IIB diversity was associated with increased Bd infection risk. On the individual level, MHC IIB heterozygotes exhibited a trend toward reduced Bd infection risk, although this was marginally non-significant. Our results suggest that habitat fragmentation increases Bd infection susceptibility in amphibians, mediated at least in part through erosion of immunogenetic diversity. Our findings have implications for management of fragmented populations in the face of emerging infectious diseases.


Assuntos
Quitridiomicetos , Micoses , Anfíbios , Animais , Anuros/genética , Brasil/epidemiologia , Ecossistema , Florestas , Imunogenética , Micoses/epidemiologia , Micoses/genética , Micoses/veterinária
4.
Bioinformatics ; 36(7): 1994-2000, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31764940

RESUMO

MOTIVATION: Whole-genome sequencing of uncultured eukaryotic genomes is complicated by difficulties in acquiring sufficient amounts of tissue. Single-cell genomics (SCG) by multiple displacement amplification provides a technical workaround, yielding whole-genome libraries which can be assembled de novo. Downsides of multiple displacement amplification include coverage biases and exacerbation of contamination. These factors affect assembly continuity and fidelity, complicating discrimination of genomes from contamination and noise by available tools. Uncultured eukaryotes and their relatives are often underrepresented in large sequence data repositories, further impairing identification and separation. RESULTS: We compare the ability of filtering approaches to remove contamination and resolve eukaryotic draft genomes from SCG metagenomes, finding significant variation in outcomes. To address these inconsistencies, we introduce a consensus approach that is codified in the SCGid software package. SCGid parallelly filters assemblies using different approaches, yielding three intermediate drafts from which consensus is drawn. Using genuine and mock SCG metagenomes, we show that our approach corrects for variation among draft genomes predicted by individual approaches and outperforms them in recapitulating published drafts in a fast and repeatable way, providing a useful alternative to available methods and manual curation. AVAILABILITY AND IMPLEMENTATION: The SCGid package is implemented in python and R. Source code is available at http://www.github.com/amsesk/SCGid under the GNU GPL 3.0 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Eucariotos , Consenso , Genoma , Genômica , Análise de Sequência de DNA , Software
5.
Mol Phylogenet Evol ; 133: 152-163, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30639767

RESUMO

Previous genome-scale phylogenetic analyses of Fungi have under sampled taxa from Zoopagales; this order contains many predacious or parasitic genera, and most have never been grown in pure culture. We sequenced the genomes of 4 zoopagalean taxa that are predators of amoebae, nematodes, or rotifers and the genome of one taxon that is a parasite of amoebae using single cell sequencing methods with whole genome amplification. Each genome was a metagenome, which was assembled and binned using multiple techniques to identify the target genomes. We inferred phylogenies with both super matrix and coalescent approaches using 192 conserved proteins mined from the target genomes and performed ancestral state reconstructions to determine the ancestral trophic lifestyle of the clade. Our results indicate that Zoopagales is monophyletic. Ancestral state reconstructions provide moderate support for mycoparasitism being the ancestral state of the clade.


Assuntos
Fungos/classificação , Fungos/genética , Genoma Fúngico , Filogenia , Animais , Sequência de Bases , Proteínas Fúngicas/genética , Biblioteca Gênica , Genômica , Funções Verossimilhança , Simbiose/genética
6.
bioRxiv ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39005276

RESUMO

Early-life immune exposures can profoundly impact lifelong health. However, functional mechanisms underlying fetal immune development remain incomplete. Erythrocytes are not typically considered active immune mediators, primarily because erythroid precursors discard their organelles as they mature, thus losing the ability to alter gene expression in response to stimuli. Erythroid progenitors and precursors circulate in human fetuses and neonates. Although there is limited evidence that erythroid precursors are immunomodulatory, our understanding of the underlying mechanisms remains inadequate. To define the immunobiological role of fetal and perinatal erythroid progenitors and precursors, we analyzed single cell RNA-sequencing data and found that transcriptomics support erythroid progenitors as putative immune mediators. Unexpectedly, we discovered that human erythroid progenitors constitutively express Major Histocompatibility Complex (MHC) class II antigen processing and presentation machinery, which are hallmarks of specialized antigen presenting immune cells. Furthermore, we demonstrate that erythroid progenitors internalize and cleave foreign proteins into peptide antigens. Unlike conventional antigen presenting cells, erythroid progenitors express atypical costimulatory molecules and immunoregulatory cytokines that direct the development of regulatory T cells, which are critical for establishing maternal-fetal tolerance. Expression of MHC II in definitive erythroid progenitors begins during the second trimester, coinciding with the appearance of mature T cells in the fetus, and is absent in primitive progenitors. Lastly, we demonstrate physical and molecular interaction potential of erythroid progenitors and T cells in the fetal liver. Our findings shed light on a unique orchestrator of fetal immunity and provide insight into the mechanisms by which erythroid cells contribute to host defense.

7.
bioRxiv ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39345402

RESUMO

Autoimmune destruction of pancreatic ß cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. Studies of human T1D immunobiology have predominantly focused on circulating immune cells in the blood, while mouse models suggest diabetogenic lymphocytes primarily reside in pancreas-draining lymph nodes (pLN). A comprehensive study of immune cells in human T1D was conducted using pancreas draining lymphatic tissues, including pLN and mesenteric lymph nodes, and the spleen from non-diabetic control, ß cell autoantibody positive non-diabetic (AAb+), and T1D organ donors using complementary approaches of high parameter flow cytometry and CITEseq. Immune perturbations suggestive of a proinflammatory environment were specific for T1D pLN and AAb+ pLN. In addition, certain immune populations correlated with high T1D genetic risk independent of disease state. These datasets form an extensive resource for profiling human lymphatic tissue immune cells in the context of autoimmunity and T1D.

8.
J Fungi (Basel) ; 8(6)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35736044

RESUMO

Glutamine synthetase (GlnS) is a key enzyme in nitrogen metabolism. We investigated the effect of the GlnS inhibitor glufosinate on the infection of H. lacustris by the blastocladialean fungus P. sedebokerense, assuming that interfering with the host nitrogen metabolism will affect the success of the parasite. Complete inhibition of infection, which could be bypassed by the GlnS product glutamine, was observed at millimolar concentrations of glufosinate. However, this effect of glufosinate was attributed to its direct interaction with the blastoclad and not the host, which results in development and growth inhibition of the blastoclad. In our P. sedebokerense draft genome, we found that the sequence of GlnS is related to another fungal GlnS, type III, found in many poor known phyla of fungi, including Blastocladiomycota and Chytridiomycota, and absent in the main subkingdom of fungi, the Dikarya. We further tested the ability of the blastoclad to utilize nitrate and ammonia as inorganic nitrogen sources and glutamine for growth. We found that P. sedebokerense equally use ammonia and glutamine and use also nitrate, but with less efficiency. Altogether, our results show that GlnS type III is mandatory for the development and growth of P. sedebokerense and could be an efficient target to develop strategies for the control of the fungal parasite of H. lacustris.

9.
Mycologia ; 111(2): 291-298, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30856068

RESUMO

Previous molecular phylogenetic studies have shown that families in Zoopagales are not monophyletic. To test the monophyly of genera and species in the order, we used a single-cell approach to generate nuclear 18S rRNA (18S) sequences for 10 isolates representing nine taxa. We provide the first sequences for the genus Zoopage and additional sequences for taxa in Cocholonema, Acaulopage, and Zoophagus. Our results reveal that Zoophagus, Zoopage, and Acaulopage tetraceros are not monophyletic. We conclude that morphology alone is not sufficient to delineate genera and species in the order and encourage studies that increase genetic sampling of taxa including type species.


Assuntos
Fungos/classificação , Fungos/genética , Filogenia , RNA Ribossômico 18S/genética , Análise de Sequência de DNA , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética
10.
IMA Fungus ; 6(2): 297-317, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26732137

RESUMO

Jimtrappea guyanensis gen. sp. nov., Castellanea pakaraimophila gen. sp. nov., and Costatisporus cyanescens gen. sp. nov. are described as new to science. These sequestrate, hypogeous fungi were collected in Guyana under closed canopy tropical forests in association with ectomycorrhizal (ECM) host tree genera Dicymbe (Fabaceae subfam. Caesalpinioideae), Aldina (Fabaceae subfam. Papilionoideae), and Pakaraimaea (Dipterocarpaceae). Molecular data place these fungi in Boletaceae (Boletales, Agaricomycetes, Basidiomycota) and inform their relationships to other known epigeous and sequestrate taxa within that family. Macro- and micromorphological characters, habitat, and multi-locus DNA sequence data are provided for each new taxon. Unique morphological features and a molecular phylogenetic analysis of 185 taxa across the order Boletales justify the recognition of the three new genera.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA