Browsing by Subject "DNA, Fungal"

Now showing 1 - 9 of 9
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    A nucleosome-guided map of transcription factor binding sites in yeast.
    (PLoS Comput Biol, 2007-11) Narlikar, Leelavati; Gordân, Raluca; Hartemink, Alexander J
    Finding functional DNA binding sites of transcription factors (TFs) throughout the genome is a crucial step in understanding transcriptional regulation. Unfortunately, these binding sites are typically short and degenerate, posing a significant statistical challenge: many more matches to known TF motifs occur in the genome than are actually functional. However, information about chromatin structure may help to identify the functional sites. In particular, it has been shown that active regulatory regions are usually depleted of nucleosomes, thereby enabling TFs to bind DNA in those regions. Here, we describe a novel motif discovery algorithm that employs an informative prior over DNA sequence positions based on a discriminative view of nucleosome occupancy. When a Gibbs sampling algorithm is applied to yeast sequence-sets identified by ChIP-chip, the correct motif is found in 52% more cases with our informative prior than with the commonly used uniform prior. This is the first demonstration that nucleosome occupancy information can be used to improve motif discovery. The improvement is dramatic, even though we are using only a statistical model to predict nucleosome occupancy; we expect our results to improve further as high-resolution genome-wide experimental nucleosome occupancy data becomes increasingly available.
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    Analyses of pediatric isolates of Cryptococcus neoformans from South Africa.
    (J Clin Microbiol, 2011-01) Miglia, Kathleen J; Govender, Nelesh P; Rossouw, Jenny; Meiring, Susan; Mitchell, Thomas G; Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa
    Compared to the incidence in adults, cryptococcosis is inexplicably rare among children, even in sub-Saharan Africa, which has the highest prevalence of coinfection with HIV and Cryptococcus neoformans. To explore any mycological basis for this age-related difference in the incidence of cryptococcosis, we investigated isolates of C. neoformans recovered from pediatric and adult patients during a 2-year period in South Africa. From reports to the Group for Enteric, Respiratory, and Meningeal Disease Surveillance in South Africa (GERMS-SA), we reviewed all cases of cryptococcosis in 2005 and 2006. We analyzed one isolate of C. neoformans from each of 82 pediatric patients (<15 years of age) and determined the multilocus sequence type (ST), mating type, ploidy, and allelic profile. This sample included isolates of all three molecular types of serotype A or C. neoformans var. grubii (molecular types VNI, VNII, and VNB) and one AD hybrid. Seventy-seven (94%) of the strains possessed the MATα mating type allele, and five were MATa. Seventy-five (91%) were haploid, and seven were diploid. A total of 24 different STs were identified. The ratios of each mating type and the proportion of haploids were comparable to those for the isolates that were obtained from 86 adult patients during the same period. Notably, the most prevalent pediatric ST was significantly associated with male patients. Overall, these pediatric isolates exhibited high genotypic diversity. They included a relatively large percentage of diploids and the rarely reported MATa mating type.
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    Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation.
    (PLoS Genet, 2014-04) Janbon, G; Ormerod, KL; Paulet, D; Byrnes, EJ; Yadav, V; Chatterjee, G; Mullapudi, N; Hon, C; Billmyre, RB; Brunel, F; Bahn, Y; Chen, W; Chen, Y; Chow, EWL; Coppée, J; Floyd-Averette, A; Gaillardin, C; Gerik, KJ; Goldberg, J; Gonzalez-Hilarion, S; Gujja, S; Hamlin, JL; Hsueh, Y; Ianiri, G; Jones, S; Kodira, CD; Kozubowski, L; Lam, W; Marra, M; Mesner, LD; Mieczkowski, PA; Moyrand, F; Nielsen, K; Proux, C; Rossignol, T; Schein, JE; Sun, S; Wollschlaeger, C; Wood, IA; Zeng, Q; Neuvéglise, C; Newlon, CS; Perfect, JR; Lodge, JK; Idnurm, A; Stajich, JE; Kronstad, JW; Sanyal, K; Heitman, J; Fraser, JA; Cuomo, CA; Dietrich, FS
    Cryptococcus neoformans is a pathogenic basidiomycetous yeast responsible for more than 600,000 deaths each year. It occurs as two serotypes (A and D) representing two varieties (i.e. grubii and neoformans, respectively). Here, we sequenced the genome and performed an RNA-Seq-based analysis of the C. neoformans var. grubii transcriptome structure. We determined the chromosomal locations, analyzed the sequence/structural features of the centromeres, and identified origins of replication. The genome was annotated based on automated and manual curation. More than 40,000 introns populating more than 99% of the expressed genes were identified. Although most of these introns are located in the coding DNA sequences (CDS), over 2,000 introns in the untranslated regions (UTRs) were also identified. Poly(A)-containing reads were employed to locate the polyadenylation sites of more than 80% of the genes. Examination of the sequences around these sites revealed a new poly(A)-site-associated motif (AUGHAH). In addition, 1,197 miscRNAs were identified. These miscRNAs can be spliced and/or polyadenylated, but do not appear to have obvious coding capacities. Finally, this genome sequence enabled a comparative analysis of strain H99 variants obtained after laboratory passage. The spectrum of mutations identified provides insights into the genetics underlying the micro-evolution of a laboratory strain, and identifies mutations involved in stress responses, mating efficiency, and virulence.
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    Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana.
    (Mol Ecol, 2015-07) Chen, Yuan; Litvintseva, Anastasia P; Frazzitta, Aubrey E; Haverkamp, Miriam R; Wang, Liuyang; Fang, Charles; Muthoga, Charles; Mitchell, Thomas G; Perfect, John R
    Cryptococcus neoformans var. grubii (Cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub-Saharan Africa. Patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. To investigate the prevalence and population structure of Cng in southern Africa, we analysed isolates from 77 environmental samples and 64 patients. We detected significant genetic diversity among isolates and strong evidence of geographic structure at the local level. High proportions of isolates with the rare MATa allele were observed in both clinical and environmental isolates; however, the mating-type alleles were unevenly distributed among different subpopulations. Nearly equal proportions of the MATa and MATα mating types were observed among all clinical isolates and in one environmental subpopulation from the eastern part of Botswana. As previously reported, there was evidence of both clonality and recombination in different geographic areas. These results provide a foundation for subsequent genomewide association studies to identify genes and genotypes linked to pathogenicity in humans.
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    Evidence that the human pathogenic fungus Cryptococcus neoformans var. grubii may have evolved in Africa.
    (PLoS One, 2011-05-11) Litvintseva, Anastasia P; Carbone, Ignazio; Rossouw, Jenny; Thakur, Rameshwari; Govender, Nelesh P; Mitchell, Thomas G
    Most of the species of fungi that cause disease in mammals, including Cryptococcus neoformans var. grubii (serotype A), are exogenous and non-contagious. Cryptococcus neoformans var. grubii is associated worldwide with avian and arboreal habitats. This airborne, opportunistic pathogen is profoundly neurotropic and the leading cause of fungal meningitis. Patients with HIV/AIDS have been ravaged by cryptococcosis--an estimated one million new cases occur each year, and mortality approaches 50%. Using phylogenetic and population genetic analyses, we present evidence that C. neoformans var. grubii may have evolved from a diverse population in southern Africa. Our ecological studies support the hypothesis that a few of these strains acquired a new environmental reservoir, the excreta of feral pigeons (Columba livia), and were globally dispersed by the migration of birds and humans. This investigation also discovered a novel arboreal reservoir for highly diverse strains of C. neoformans var. grubii that are restricted to southern Africa, the mopane tree (Colophospermum mopane). This finding may have significant public health implications because these primal strains have optimal potential for evolution and because mopane trees contribute to the local economy as a source of timber, folkloric remedies and the edible mopane worm.
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    ItemRestricted
    Evidence-ranked motif identification.
    (Genome Biol, 2010) Georgiev, S; Boyle, AP; Jayasurya, K; Ding, X; Mukherjee, Sayan; Ohler, Uwe
    cERMIT is a computationally efficient motif discovery tool based on analyzing genome-wide quantitative regulatory evidence. Instead of pre-selecting promising candidate sequences, it utilizes information across all sequence regions to search for high-scoring motifs. We apply cERMIT on a range of direct binding and overexpression datasets; it substantially outperforms state-of-the-art approaches on curated ChIP-chip datasets, and easily scales to current mammalian ChIP-seq experiments with data on thousands of non-coding regions.
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    Pulmonary blastomycosis presenting as primary lung cancer.
    (BMC infectious diseases, 2018-07-18) Hussaini, Syed Mohammed Qasim; Madut, Deng; Tong, Betty C; Pavlisko, Elizabeth N; Schell, Wiley A; Perfect, John R; Thielman, Nathan M
    BACKGROUND:Blastomycosis is an endemic mycosis in North America that is caused by the dimorphic fungus Blastomyces dermatitidis. The illness is a systemic disease with a wide variety of pulmonary and extra-pulmonary manifestations. The initial presentation of blastomycosis may easily be mistaken for other infectious or non-infectious etiologies. CASE PRESENTATION:We present the case of a 52-year-old African-American male and former smoker that presented to his primary care provider with a 2-week history of non-productive cough, night sweats and weight loss. Initially diagnosed with primary lung malignancy, the patient was subsequently found to have pulmonary blastomycosis mimicking lung cancer. The patient underwent a successful course of treatment with posaconazole. CONCLUSIONS:Chronic blastomycosis can present with clinical and radiographic features indistinguishable from thoracic malignancies. There is no clinical syndrome specific for blastomycosis, thus a high degree of suspicion is required for early diagnosis. In this case report, we review recent evidence in radiographic features, diagnostic considerations and treatment of the disease.
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    Structure, function, and phylogeny of the mating locus in the Rhizopus oryzae complex.
    (PLoS One, 2010-12-09) Gryganskyi, AP; Lee, SC; Litvintseva, AP; Smith, ME; Bonito, G; Porter, TM; Anishchenko, IM; Heitman, J; Vilgalys, R
    The Rhizopus oryzae species complex is a group of zygomycete fungi that are common, cosmopolitan saprotrophs. Some strains are used beneficially for production of Asian fermented foods but they can also act as opportunistic human pathogens. Although R. oryzae reportedly has a heterothallic (+/-) mating system, most strains have not been observed to undergo sexual reproduction and the genetic structure of its mating locus has not been characterized. Here we report on the mating behavior and genetic structure of the mating locus for 54 isolates of the R. oryzae complex. All 54 strains have a mating locus similar in overall organization to Phycomyces blakesleeanus and Mucor circinelloides (Mucoromycotina, Zygomycota). In all of these fungi, the minus (-) allele features the SexM high mobility group (HMG) gene flanked by an RNA helicase gene and a TP transporter gene (TPT). Within the R. oryzae complex, the plus (+) mating allele includes an inserted region that codes for a BTB/POZ domain gene and the SexP HMG gene. Phylogenetic analyses of multiple genes, including the mating loci (HMG, TPT, RNA helicase), ITS1-5.8S-ITS2 rDNA, RPB2, and LDH genes, identified two distinct groups of strains. These correspond to previously described sibling species R. oryzae sensu stricto and R. delemar. Within each species, discordant gene phylogenies among multiple loci suggest an outcrossing population structure. The hypothesis of random-mating is also supported by a 50:50 ratio of plus and minus mating types in both cryptic species. When crossed with tester strains of the opposite mating type, most isolates of R. delemar failed to produce zygospores, while isolates of R. oryzae produced sterile zygospores. In spite of the reluctance of most strains to mate in vitro, the conserved sex locus structure and evidence for outcrossing suggest that a normal sexual cycle occurs in both species.
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    Two new endophytic Atractiellomycetes, Atractidochium hillariae and Proceropycnis hameedii.
    (Mycologia, 2018-01) Aime, M Catherine; Urbina, Hector; Liber, Julian A; Bonito, Gregory; Oono, Ryoko
    Sterile fungal isolates are often recovered in leaf and root endophytic studies, although these seldom play a significant role in downstream analyses. The authors sought to identify and characterize two such endophytes-one representing the most commonly recovered fungal isolate in recent studies of needle endophytes of Pinus taeda and the other representing a rarely isolated root endophyte of Populus trichocarpa. Both are shown by DNA sequencing to be undescribed species of Atractiellomycetes (Pucciniomycotina, Basidiomycota), a poorly characterized class of mostly plant-associated and presumably saprobic microfungi. The authors describe the new genus and species Atractidochium hillariae (Phleogenaceae) and the new species Proceropycnis hameedii (Hoehnelomycetaceae), both in the Atractiellales, to accommodate these unusual isolates. Following incubations of 1-2 mo, A. hillariae produces minute white sporodochia, similar to those produced by several other members of Atractiellales, whereas Pr. hameedii forms conidia singly or in chains in a manner similar to its sister species Pr. pinicola. Additionally, we provide a taxonomic revision of Atractiellomycetes based on multilocus analyses and propose the new genera Neogloea (Helicogloeaceae) and Bourdotigloea (Phleogenaceae) to accommodate ex-Helicogloea species that are not congeneric with the type H. lagerheimii. Atractiellomycetes consists of a single order, Atractiellales, and three families, Hoehnelomycetaceae, Phleogenaceae, and Helicogloeaceae. Accumulated evidence suggests that Atractiellomycetes species are common but infrequently isolated members of plant foliar and root endobiomes.