Comparative Genome Structure, Secondary Metabolite, and Effector Coding Capacity across Cochliobolus Pathogens

Condon, Bradford; Leng, Yueqiang; Wu, Dongliang; Bushley, Kathryn E.; Ohm, Robin A.; Otillar, Robert; Martin, Joel; Schackwitz, Wendy; Grimwood, Jane; Zainudin, Nur Ain Izzati Mohd; Xue, Chunsheng; Wang, Rui; Manning, Viola A.; Dhillon, Braham; Tu, Zheng Jin; Steffenson, Brian J.; Salamov, Asaf; Sun, Hui; Lowry, Steve; LaButti, Kurt; Han, James; Copeland, Alex; Lindquist, Erika; Barry, Kerrie; Schmutz, Jeremy; Baker, Scott E.; Ciuffetti, Lynda M.; Grigoriev, Igor V.; Zhong, Shaobin; Turgeon, B. Gillian

doi:10.1371/journal.pgen.1003233

Cited by 212 publications

(223 citation statements)

References 108 publications

(175 reference statements)

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“…Besides the core catalytic enzymes that assemble monomeric units, these complexes may include genes involved in precursor biosynthesis, regulation, resistance, and transport. Mapping the phylogenetic distributions of biosynthetic pathway genes across fungal genomes has provided new insights into the origins of these gene clusters and how they evolved to elaborate the chemical diversity so characteristic of higher fungi, while correlation of these patterns with life histories has offered clues about their natural functions (1)(2)(3)(4).…”

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confidence: 99%

Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

Yue

Chen

et al. 2015

Eukaryot Cell

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The echinocandins are a class of antifungal drugs that includes caspofungin, micafungin, and anidulafungin. Gene clusters encoding most of the structural complexity of the echinocandins provided a framework for hypotheses about the evolutionary history and chemical logic of echinocandin biosynthesis. Gene orthologs among echinocandin-producing fungi were identified. Pathway genes, including the nonribosomal peptide synthetases (NRPSs), were analyzed phylogenetically to address the hypothesis that these pathways represent descent from a common ancestor. The clusters share cooperative gene contents and linkages among the different strains. Individual pathway genes analyzed in the context of similar genes formed unique echinocandinexclusive phylogenetic lineages. The echinocandin NRPSs, along with the NRPS from the inp gene cluster in Aspergillus nidulans and its orthologs, comprise a novel lineage among fungal NRPSs. NRPS adenylation domains from different species exhibited a one-to-one correspondence between modules and amino acid specificity that is consistent with models of tandem duplication and subfunctionalization. Pathway gene trees and Ascomycota phylogenies are congruent and consistent with the hypothesis that the echinocandin gene clusters have a common origin. The disjunct Eurotiomycete-Leotiomycete distribution appears to be consistent with a scenario of vertical descent accompanied by incomplete lineage sorting and loss of the clusters from most lineages of the Ascomycota. We present evidence for a single evolutionary origin of the echinocandin family of gene clusters and a progression of structural diversification in two fungal classes that diverged approximately 290 to 390 million years ago. Lineagespecific gene cluster evolution driven by selection of new chemotypes contributed to diversification of the molecular functionalities.

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confidence: 99%

Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

Yue

Chen

et al. 2015

Eukaryot Cell

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“…7a). As previously described, 6,54 three other putative genes have been identified adjacent to the MAT1-2 : (i) a β-glucosidase homolog gene (3′ flank of MAT1-2 ), (ii) a homolog of a yeast gene (ORF1) with unknown function (5′ flank of MAT1-2 ) and (iii) a GTPase-activating homolog gene (5′ flank of MAT1-2 ) (Fig. 7a).…”

Section: Resultsmentioning

confidence: 67%

“…Like most Cochliobolus plant pathogens reported, 6 B. papendorfii UM 226 is enriched with multidomain NRPS encoding genes (NPS) and PKS genes. NPS2 (UM226_2338, 74% identical), NPS6 (UM226_3398, 87% identical), NPS4 (UM226_5568, 82% identical) and NPS10 (UM226_3258, 93% identical) orthologous genes found in B. papendorfii UM 226 were reported to be conserved across all Cochliobolus species.…”

Section: Resultsmentioning

confidence: 99%

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Dissecting the fungal biology of Bipolaris papendorfii: from phylogenetic to comparative genomic analysis

et al. 2015

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Bipolaris papendorfii has been reported as a fungal plant pathogen that rarely causes opportunistic infection in humans. Secondary metabolites isolated from this fungus possess medicinal and anticancer properties. However, its genetic fundamental and basic biology are largely unknown. In this study, we report the first draft genome sequence of B. papendorfii UM 226 isolated from the skin scraping of a patient. The assembled 33.4 Mb genome encodes 11,015 putative coding DNA sequences, of which, 2.49% are predicted transposable elements. Multilocus phylogenetic and phylogenomic analyses showed B. papendorfii UM 226 clustering with Curvularia species, apart from other plant pathogenic Bipolaris species. Its genomic features suggest that it is a heterothallic fungus with a putative unique gene encoding the LysM-containing protein which might be involved in fungal virulence on host plants, as well as a wide array of enzymes involved in carbohydrate metabolism, degradation of polysaccharides and lignin in the plant cell wall, secondary metabolite biosynthesis (including dimethylallyl tryptophan synthase, non-ribosomal peptide synthetase, polyketide synthase), the terpenoid pathway and the caffeine metabolism. This first genomic characterization of B. papendorfii provides the basis for further studies on its biology, pathogenicity and medicinal potential.

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“…A further phylogenetic study of these organisms at the whole-genome level as well as detailed morphological and physiological analyses of different genetic groups will be needed to determine potential species boundaries. The genome of another closely related species, Exserohilum turcicum, has recently been released (36), but the genome size difference alone (43 Mb versus 33.8 Mb) shows just how much diversity lies within this group of organisms and indicates that more research in needed to understand the phylogeny of Exserohilum.…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Analysis of Exserohilum rostratum from an Outbreak of Fungal Meningitis and Other Infections

et al. 2014

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Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ϳ136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum. Beginning in September, 2012, the United States experienced one of the largest outbreaks of health care-associated infections ever reported. More than 13,000 people were exposed to three lots of contaminated methylprednisolone acetate (MPA) produced by a single compounding pharmacy, and Ͼ750 developed fungal infections following their MPA injections (1-3). Infections included meningitis, as well as localized epidural, paraspinal, and peripheral joint infections, complicated by arachnoiditis and abscess formation (4, 5). Although several fungal species were implicated in the outbreak, the vast majority of infections were caused by Exserohilum rostratum, a saprobic mold found in soil and plant debris worldwide (2, 6-10). Most species of Exserohilum are plant pathogens. Exserohilum rostratum and the species formerly known as Exserohilum longirostratum and Exserohilum mcginnisii are morphologically similar and are the only species known to cause human infections; however, their taxonomic status remains under investigation (11-13).DNA fingerprinting has been used as an epidemiological tool to answer questions pertaining to strain relatedness (14, 15). However, no methodologies for DNA fingerprinting of E. rostratum existed at the time of the outbreak. While whole-genome sequencing (WGS) is a relatively new tool of molecular epidemiology, it has quickly been embraced as a mechanism for inferring phylogenetic relationships among organisms. This has translated to the recent use of whole-genome single nucleotide polymorphism (SNP) typing (whole-genome sequence typing [WGST]) as a mechanism for inferring relatedness of both bacteria (16)(17)(18)(19) and fungi (20, 21) during outbreak investigations. One of the benefits of WGST is that prior knowledge of the genome i...

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Comparative Genome Structure, Secondary Metabolite, and Effector Coding Capacity across Cochliobolus Pathogens

Cited by 212 publications

References 108 publications

Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

Evolution of Chemical Diversity in Echinocandin Lipopeptide Antifungal Metabolites

Dissecting the fungal biology of Bipolaris papendorfii: from phylogenetic to comparative genomic analysis

Whole-Genome Analysis of Exserohilum rostratum from an Outbreak of Fungal Meningitis and Other Infections

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