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Background Secondary metabolite production, a hallmark of filamentous fungi, is an expanding area of research for the Aspergilli. These compounds are potent chemicals, ranging from deadly toxins to therapeutic antibiotics to potential anti-cancer drugs. The genome sequences for multiple Aspergilli have been determined, and provide a wealth of predictive information about secondary metabolite production. Sequence analysis and gene overexpression strategies have enabled the discovery of novel secondary metabolites and the genes involved in their biosynthesis. The Aspergillus Genome Database (AspGD) provides a central repository for gene annotation and protein information for Aspergillus species. These annotations include Gene Ontology (GO) terms, phenotype data, gene names and descriptions and they are crucial for interpreting both small- and large-scale data and for aiding in the design of new experiments that further Aspergillus research. Results We have manually curated Biological Process GO annotations for all genes in AspGD with recorded functions in secondary metabolite production, adding new GO terms that specifically describe each secondary metabolite. We then leveraged these new annotations to predict roles in secondary metabolism for genes lacking experimental characterization. As a starting point for manually annotating Aspergillus secondary metabolite gene clusters, we used antiSMASH (antibiotics and Secondary Metabolite Analysis SHell) and SMURF (Secondary Metabolite Unknown Regions Finder) algorithms to identify potential clusters in A. nidulans , A. fumigatus, A. niger and A. oryzae , which we subsequently refined through manual curation. Conclusions This set of 266 manually curated secondary metabolite gene clusters will facilitate the investigation of novel Aspergillus secondary metabolites.

The degree to which molecular epidemiology reveals information about the sources and transmission patterns of an outbreak depends on the resolution of the technology used and the samples studied. Isolates of Escherichia coli O104:H4 from the outbreak centered in Germany in May–July 2011, and the much smaller outbreak in southwest France in June 2011, were indistinguishable by standard tests. We report a molecular epidemiological analysis using multiplatform whole-genome sequencing and analysis of multiple isolates from the German and French outbreaks. Isolates from the German outbreak showed remarkably little diversity, with only two single nucleotide polymorphisms (SNPs) found in isolates from four individuals. Surprisingly, we found much greater diversity (19 SNPs) in isolates from seven individuals infected in the French outbreak. The German isolates form a clade within the more diverse French outbreak strains. Moreover, five isolates derived from a single infected individual from the French outbreak had extremely limited diversity. The striking difference in diversity between the German and French outbreak samples is consistent with several hypotheses, including a bottleneck that purged diversity in the German isolates, variation in mutation rates in the two E. coli outbreak populations, or uneven distribution of diversity in the seed populations that led to each outbreak.

The human malaria parasite Plasmodium vivax is responsible for 25–40% of the ∼515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species. MALARIA PARASITES: New Plasmodium sequences kick-start comparative genomics Four distinct Plasmodium species are known to regularly infect humans: Plasmodium falciparum , P. vivax , P. malariae and P. ovale . The genome sequence of P. falciparum , the cause of the most severe type of human malaria, was completed in 2002 at the same time as the mosquito vector, Anopheles gambiae . In this week's Nature , which focuses on the malaria parasite, two further malaria genome sequences are described. First that of P. vivax , which contributes significant numbers to malaria incidence in humans, though in contrast to P. falciparum , the resulting disease is usually not fatal. The genome of this rather neglected species is presented together with a comparative analysis with the genomes of other Plasmodium species. Second, we publish the genome sequence of Plasmodium knowlesi . For long regarded as a monkey malaria parasite, it is increasingly becoming recognized as the fifth human-infecting Plasmodium species. In particular, it is prevalent in South East Asia where it is often misdiagnosed as another human malaria parasite P. malariae . As a model organism P. knowlesi stands out: not only is it a primate system, useful for work on vaccines, but it can be cultured in vitro and subjected to efficient transfection and gene knockouts. In a Review Article, Elizabeth Winzeler considers the progress made towards using the genome sequence to understand basic malaria parasite biology, and in particular the work on developing rational therapeutic approaches to combat P. falciparum infections. See also the Editorial. For a comprehensive collection of resources visit Nature 's past malaria specials: Malaria killer blow ; Outlook on malaria ; Malaria web focus ; Malaria Insight ; Nature Medicine focus on malaria ; Focus on malaria

Thomas Nutman and colleagues report the draft genome of the filarial pathogen Loa loa , the African eyeworm. They also report coverage of two other filarial pathogens, Wuchereria bancrofti and Onchocerca volvulus . Unlike most filariae, L. loa lacks an obligate intracellular Wolbachia endosymbiont, and comparative genomic analyses suggest that the L. loa genome does not contain new metabolic synthesis or transport pathways compared to other filariae. Loa loa , the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae, L. loa does not contain the obligate intracellular Wolbachia endosymbiont. We describe the 91.4-Mb genome of L. loa and that of the related filarial parasite Wuchereria bancrofti and predict 14,907 L. loa genes on the basis of microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite, Brugia malayi , and to those of several other nematodes, we demonstrate synteny among filariae but not with nonparasitic nematodes. The L. loa genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for use in humans. Despite lacking Wolbachia , L. loa shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role of Wolbachia in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and nonparasitic nematodes.

We present the genome sequences of a new clinical isolate of the important human pathogen, Aspergillus fumigatus, A1163, and two closely related but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of A1163 with the recently sequenced A. fumigatus isolate Af293 has identified core, variable and up to 2% unique genes in each genome. While the core genes are 99.8% identical at the nucleotide level, identity for variable genes can be as low 40%. The most divergent loci appear to contain heterokaryon incompatibility (het) genes associated with fungal programmed cell death such as developmental regulator rosA. Cross-species comparison has revealed that 8.5%, 13.5% and 12.6%, respectively, of A. fumigatus, N. fischeri and A. clavatus genes are species-specific. These genes are significantly smaller in size than core genes, contain fewer exons and exhibit a subtelomeric bias. Most of them cluster together in 13 chromosomal islands, which are enriched for pseudogenes, transposons and other repetitive elements. At least 20% of A. fumigatus-specific genes appear to be functional and involved in carbohydrate and chitin catabolism, transport, detoxification, secondary metabolism and other functions that may facilitate the adaptation to heterogeneous environments such as soil or a mammalian host. Contrary to what was suggested previously, their origin cannot be attributed to horizontal gene transfer (HGT), but instead is likely to involve duplication, diversification and differential gene loss (DDL). The role of duplication in the origin of lineage-specific genes is further underlined by the discovery of genomic islands that seem to function as designated \"gene dumps\" and, perhaps, simultaneously, as \"gene factories\".

The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally. Non-standard outcomes of rearrangement events, including the generation of short-lived somatic chromosomes and excision of DNA interrupting protein-coding regions, may represent novel forms of developmental gene regulation. We also compare Tetrahymena’s germline/soma differentiation to that of other characterized ciliates, illustrating the wide diversity of adaptations that have occurred within this phylum.

Secondary metabolites, including toxins and melanins, have been implicated as virulence attributes in invasive aspergillosis. Although not definitively proved, this supposition is supported by the decreased virulence of an Aspergillus fumigatus strain, DeltalaeA, that is crippled in the production of numerous secondary metabolites. However, loss of a single LaeA-regulated toxin, gliotoxin, did not recapitulate the hypovirulent DeltalaeA pathotype, thus implicating other toxins whose production is governed by LaeA. Toward this end, a whole-genome comparison of the transcriptional profile of wild-type, DeltalaeA, and complemented control strains showed that genes in 13 of 22 secondary metabolite gene clusters, including several A. fumigatus-specific mycotoxin clusters, were expressed at significantly lower levels in the DeltalaeA mutant. LaeA influences the expression of at least 9.5% of the genome (943 of 9,626 genes in A. fumigatus) but positively controls expression of 20% to 40% of major classes of secondary metabolite biosynthesis genes such as nonribosomal peptide synthetases (NRPSs), polyketide synthases, and P450 monooxygenases. Tight regulation of NRPS-encoding genes was highlighted by quantitative real-time reverse-transcription PCR analysis. In addition, expression of a putative siderophore biosynthesis NRPS (NRPS2/sidE) was greatly reduced in the DeltalaeA mutant in comparison to controls under inducing iron-deficient conditions. Comparative genomic analysis showed that A. fumigatus secondary metabolite gene clusters constitute evolutionarily diverse regions that may be important for niche adaptation and virulence attributes. Our findings suggest that LaeA is a novel target for comprehensive modification of chemical diversity and pathogenicity.

A major challenge with the treatment of Clostridioides difficile infection is restoring the antibiotic-associated alterations of bowel flora to a state less hospitable to C. difficile . In this trial, a microbiome-replacement therapy, SER-109, was used to treat patients with recurrent C. difficile infection and was shown to reduce the risk of further recurrence.

The large outbreak of diarrhea and hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli O104:H4 in Europe from May to July 2011 highlighted the potential of a rarely identified E. coli serogroup to cause severe disease. Prior to the outbreak, there were very few reports of disease caused by this pathogen and thus little known of its diversity and evolution. The identification of cases of HUS caused by E. coli O104:H4 in France and Turkey after the outbreak and with no clear epidemiological links raises questions about whether these sporadic cases are derived from the outbreak. Here, we report genome sequences of five independent isolates from these cases and results of a comparative analysis with historical and 2011 outbreak isolates. These analyses revealed that the five isolates are not derived from the outbreak strain; however, they are more closely related to the outbreak strain and each other than to isolates identified prior to the 2011 outbreak. Over the short time scale represented by these closely related organisms, the majority of genome variation is found within their mobile genetic elements: none of the nine O104:H4 isolates compared here contain the same set of plasmids, and their prophages and genomic islands also differ. Moreover, the presence of closely related HUS-associated E. coli O104:H4 isolates supports the contention that fully virulent O104:H4 isolates are widespread and emphasizes the possibility of future food-borne E. coli O104:H4 outbreaks. IMPORTANCE In the summer of 2011, a large outbreak of bloody diarrhea with a high rate of severe complications took place in Europe, caused by a previously rarely seen Escherichia coli strain of serogroup O104:H4. Identification of subsequent infections caused by E. coli O104:H4 raised questions about whether these new cases represented ongoing transmission of the outbreak strain. In this study, we sequenced the genomes of isolates from five recent cases and compared them with historical isolates. The analyses reveal that, in the very short term, evolution of the bacterial genome takes place in parts of the genome that are exchanged among bacteria, and these regions contain genes involved in adaptation to local environments. We show that these recent isolates are not derived from the outbreak strain but are very closely related and share many of the same disease-causing genes, emphasizing the concern that these bacteria may cause future severe outbreaks. In the summer of 2011, a large outbreak of bloody diarrhea with a high rate of severe complications took place in Europe, caused by a previously rarely seen Escherichia coli strain of serogroup O104:H4. Identification of subsequent infections caused by E. coli O104:H4 raised questions about whether these new cases represented ongoing transmission of the outbreak strain. In this study, we sequenced the genomes of isolates from five recent cases and compared them with historical isolates. The analyses reveal that, in the very short term, evolution of the bacterial genome takes place in parts of the genome that are exchanged among bacteria, and these regions contain genes involved in adaptation to local environments. We show that these recent isolates are not derived from the outbreak strain but are very closely related and share many of the same disease-causing genes, emphasizing the concern that these bacteria may cause future severe outbreaks.

Castor beans are best known as a source of industrial lubricants and the toxic bioterror threat, ricin, and they have potential to provide biofuel. Chan et al . present the draft sequence of the Ricinus communis genome, the first for a member of the Euphorbiaceae. Castor bean ( Ricinus communis ) is an oilseed crop that belongs to the spurge (Euphorbiaceae) family, which comprises ∼6,300 species that include cassava ( Manihot esculenta ), rubber tree ( Hevea brasiliensis ) and physic nut ( Jatropha curcas ). It is primarily of economic interest as a source of castor oil, used for the production of high-quality lubricants because of its high proportion of the unusual fatty acid ricinoleic acid. However, castor bean genomics is also relevant to biosecurity as the seeds contain high levels of ricin, a highly toxic, ribosome-inactivating protein. Here we report the draft genome sequence of castor bean (4.6-fold coverage), the first for a member of the Euphorbiaceae. Whereas most of the key genes involved in oil synthesis and turnover are single copy, the number of members of the ricin gene family is larger than previously thought. Comparative genomics analysis suggests the presence of an ancient hexaploidization event that is conserved across the dicotyledonous lineage.