Category Archives: candida

2012 Fungal Genomes: a review of mycological genomic accomplishments

2012 was certainly a banner year in genome sequence production and publications. The cost of generating the data keeps dropping and the automation for assembly and annotation continues to improve making it possible for a range of groups to publish genomes.

I made a NCBI PubMed Collection of these here Fungal Genomes 2012

Some notable fungal genome publications include

There were also several new insights into the evolution of wood decay fungi derived from new genomes of basidiomycete fungi. This includes

(Now I might have missed a few in my attempt to get this done before holidays overtake me – if so, please post comments or tweets and I’ll be sure to amend the list on pubmed and here.)

A new trend for fungal genome papers can be seen now in the Genome Announcements of Eukaryotic Cell which aim to get the genome data out quickly with a citateable reference. These are short descriptions which I expect will become more popular ways to insure data made public can also be cited. I only counted about 5 published in 2012 but I expect to see a lot more of these in the 2013 either at EC or other journals. I’m sure there will still be some tension between providers making data public as soon as possible and the sponsoring authors’ desire to have first crack at analyzing and publish interpretations and comparison of the genome(s). The bacterial community has been doing this for Genome Reports in the SIGS journal and the Journal of Bacteriology so will see what happens as these small eukaryotic genomes become even easier to produce.

I look forward to exciting year with more of the 1000 Fungal genomes and other JGI  projects start to roll out more genomes.  I also predict there will be many more resequencing datasets published as functional and population genomics. It will also probably be a countdown for what are the last Sanger sequenced genomes and how the many flavors of next generation sequencing will be optimized for generation.  I am hopeful work on automation of annotation and comparisons will be even easier for more people to use and that we start to provide a shared repository of gene predictions.  I’ve just launched the latter and look forward to engaging more people to contribute to this.

A cacophony of comparative genomics papers

A nice series of comparative genomics articles have been published in the last few weeks. The pace of genome sequencing has accelerated to the point that we have lots of sequencing projects coming from individual labs and small consortia not necessarily from genome centers. We are seeing a preview of what next (2nd) generation sequencing will enable and can start to imagine what happens when even cheaper 3rd generation sequencing technologies are applied. I’m behind in reviewing these papers for you, dear reader, but I hope you’ll click through and take a look at some of these papers if you are interested in the topics.

In the following set of papers we have some nice examples of comparative genomics of closely related species and among a clade of species. The papers mentioned below include our work on the human pathogens Coccidioides and Histoplasma (Sharpton et al) studied at several evolutionary distances, a study on Saccharomycetaceae (Souciet et al) clade of yeast species, and a comparison of two species of Candida (Jackson et al): the commensal and opportunistic fungal pathogen Candida albicans with a very closely related species Candida dubliensis.  There is also a nice comparison of strains of Saccharomyces cerevisiae looking at effects of domestication and examples of horizontal transfer.

There is also a report of de novo sequencing of a filamentous fungus using several approaches, traditional Sanger sequencing, 454, and Illumina/Solexa (DiGuistini et al).

Finally, a paper from a few months ago (Ma et al), gives a fantastic look at one of the early branches in the fungal tree – the Mucorales (formerly Zygomycota) – via the genome of Rhizopus oryzae.  This paper is a really excellent example of what we can learn about a group of species by contrasting genomic features in the early branches in the tree with the more well studied Ascomycete and Basidiomycete fungi.  More genome sequences will help us build on these findings and clarify if some of the observations are unique to the lineage or universal aspects of the earliest fungi.

I hope you enjoy!

Novo, M., Bigey, F., Beyne, E., Galeote, V., Gavory, F., Mallet, S., Cambon, B., Legras, J., Wincker, P., Casaregola, S., & Dequin, S. (2009). Eukaryote-to-eukaryote gene transfer events revealed by the genome sequence of the wine yeast Saccharomyces cerevisiae EC1118 Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0904673106 (via J Heitman)

Jackson, A., Gamble, J., Yeomans, T., Moran, G., Saunders, D., Harris, D., Aslett, M., Barrell, J., Butler, G., Citiulo, F., Coleman, D., de Groot, P., Goodwin, T., Quail, M., McQuillan, J., Munro, C., Pain, A., Poulter, R., Rajandream, M., Renauld, H., Spiering, M., Tivey, A., Gow, N., Barrell, B., Sullivan, D., & Berriman, M. (2009). Comparative genomics of the fungal pathogens Candida dubliniensis and C. albicans Genome Research DOI: 10.1101/gr.097501.109

DiGuistini, S., Liao, N., Platt, D., Robertson, G., Seidel, M., Chan, S., Docking, T., Birol, I., Holt, R., Hirst, M., Mardis, E., Marra, M., Hamelin, R., Bohlmann, J., Breuil, C., & Jones, S. (2009). De novo genome sequence assembly of a filamentous fungus using Sanger, 454 and Illumina sequence data. Genome Biology, 10 (9) DOI: 10.1186/gb-2009-10-9-r94 (open access)

Sharpton, T., Stajich, J., Rounsley, S., Gardner, M., Wortman, J., Jordar, V., Maiti, R., Kodira, C., Neafsey, D., Zeng, Q., Hung, C., McMahan, C., Muszewska, A., Grynberg, M., Mandel, M., Kellner, E., Barker, B., Galgiani, J., Orbach, M., Kirkland, T., Cole, G., Henn, M., Birren, B., & Taylor, J. (2009). Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives Genome Research DOI: 10.1101/gr.087551.108 (open access)

Souciet, J., Dujon, B., Gaillardin, C., Johnston, M., Baret, P., Cliften, P., Sherman, D., Weissenbach, J., Westhof, E., Wincker, P., Jubin, C., Poulain, J., Barbe, V., Segurens, B., Artiguenave, F., Anthouard, V., Vacherie, B., Val, M., Fulton, R., Minx, P., Wilson, R., Durrens, P., Jean, G., Marck, C., Martin, T., Nikolski, M., Rolland, T., Seret, M., Casaregola, S., Despons, L., Fairhead, C., Fischer, G., Lafontaine, I., Leh, V., Lemaire, M., de Montigny, J., Neuveglise, C., Thierry, A., Blanc-Lenfle, I., Bleykasten, C., Diffels, J., Fritsch, E., Frangeul, L., Goeffon, A., Jauniaux, N., Kachouri-Lafond, R., Payen, C., Potier, S., Pribylova, L., Ozanne, C., Richard, G., Sacerdot, C., Straub, M., & Talla, E. (2009). Comparative genomics of protoploid Saccharomycetaceae Genome Research DOI: 10.1101/gr.091546.109 (open access)

Ma, L., Ibrahim, A., Skory, C., Grabherr, M., Burger, G., Butler, M., Elias, M., Idnurm, A., Lang, B., Sone, T., Abe, A., Calvo, S., Corrochano, L., Engels, R., Fu, J., Hansberg, W., Kim, J., Kodira, C., Koehrsen, M., Liu, B., Miranda-Saavedra, D., O’Leary, S., Ortiz-Castellanos, L., Poulter, R., Rodriguez-Romero, J., Ruiz-Herrera, J., Shen, Y., Zeng, Q., Galagan, J., Birren, B., Cuomo, C., & Wickes, B. (2009). Genomic Analysis of the Basal Lineage Fungus Rhizopus oryzae Reveals a Whole-Genome Duplication PLoS Genetics, 5 (7) DOI: 10.1371/journal.pgen.1000549 (open access)

For your reading pleasure

Too much on my plate as of late, so I’m woefully behind on posting much on interesting papers or news.  Here’s a short list of links and papers that are worth a look though.

  • “Evolution of pathogenicity and sexual reproduction in eight Candida genomes” published (Nature)
  • NYT Science article sort of summarizing the good, bad, and ugly of fungi and human interactions
  • Attempts to save amphibians from chytridiomycosis “Riders of a Modern-Day Ark” (PLoS Biology)
  • Looks like Scott Baker with the JGI are in the process of resequencing several classical mutant strains of Phycomyces, Neurospora and Cochliobolus, Cryphonectria for sequence-based mapping of mutants (i.e. here and here and here).

Candida White-Opaque switching

Blogging on Peer-Reviewed ResearchA paper in PLoS Biology from Sandy Johnson’s lab entitled “Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans discusses phenotype switching in the human pathogenic fungus Candida albicans. Why is the important?

“White-opaque switching is an epigenetic phenomenon, where genetically identical cells can exist in two distinctive cell types, white and opaque. Each cell type is stably inherited for many generations, and switching between the two types of cells occurs stochastically and rarely—roughly one switch in 10^4 cell divisions”

white-opaque coloniesThere is also a review by Kira O’Day to discuss the implications of the findings. Understanding this sort of developmental and epigenetic signaling is important to better know how fungi adjust and interact with their environment. However, the authors do conclude that White-Opaque switching is exclusive to Candida albicans so aspects of this research only directly applicable to studies in this system. Phenotype switching is an active area of research for Candida biologists – some nice micrographs and SEM of the different cell morphologies can be seen at Prof. Joachim Morschhäuser’s page (and linked to the right).

Continue reading Candida White-Opaque switching

Exploring CUG codon evolution in Candida

A recent PLoS One article “A Genetic Code Alteration Is a Phenotype Diversity Generator in the Human Pathogen Candida albicans” finds some pretty dramatic changes in gene expression and phenotypes by replacing the tRNAs for CUG back to Leucine (Leu; in the standard genetic code) from their meaning of Serine (Ser) in these Candida species. The CUG codon transition in some Candida spp has been of interest since it is an example of a recent change in the genetic code and provides a comparative system to study the mechanism and genome changes of how a genetic code shift is manifested.

Continue reading Exploring CUG codon evolution in Candida

Gene knockouts in Candida parapsilosis

Cparapsilosis from G.ButlerA recent paper “Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence”, from the Nosanchuk lab at Yeshiva University, shows the role of secreted lipases in virulence of this pathogen. C. parapsilosis is second only to the evolutionarily closely related commensal Candida albicans as worldwide cause of invasive candidiasis. This paper demonstrates a knockout system using selectable marker which confers resistance to the drug Nourseothricin. The authors sought to delete the adjacent and convergently-transcribed lipase genes CpLIP1 and CpLIP2 and characterize the phenotype of the lipase deficient mutants as blood-borne C. parapsilosis infections are in a lipid rich environment.

Through a series of experiments testing growth in rich media, media with olive-oil, and in infection models they showed that the importance of lipase activity. The knockout strain was unable to grow efficiently on YNB media+olive oil indicating that these two genes are the only ones capable of lipase activity. The murine infection experiments indicated that the knockout could be cleared in 4 days while the WT and reconstituted were cleared in 7. The authors acknowledge some limitations in the infection model in that it does not fully recapitulate an invasive candidiasis because mice were infected intravenously so the role of endothelial cell invasion was tested in vivo.

This is not the first paper on targeted gene knockouts in this fungus. A paper from earlier this summer, “Development of a gene knockout system in Candida parapsilosis reveals a conserved role for BCR1 in biofilm formation”, from Geraldine Butler’s group at University College group, who work on both evolutionary and pathogenesis questions in Candida species, developed a knockout system using the same drug marker. The Butler laboratory also showed that the C. parapsilosis MAT locus, part of the sexual reproduction machinery of fungi, has degraded, consistent with the observed asexuality of these species.

The improving genetic tools for targeted disruption of loci in additional species is permitting experiments that get at the heart of what makes some fungi pathogenic. With the genome sequence of many of the relatives of the pathogens we can systematically dissect what genetic differences have a role in virulence. It will be interesting to reconstruct whether the ancestor of many of these Candida spp always had the potential for virulence or if it co-evolved with its human or other mammalian commensal lifestyle.

Genome resources for Candida species

The Candida clade of Hemiascomycete fungi have received much attention from funding bodies so that many genomic and experimental resources are available address questions of pathogenecity and industrial applications of these species.

The Candida genus

Traditionally, species of yeasts that were thought to be asexual were given the genus name Candida. This has lead to Candida being a sort of taxonomic rubbish bin as this system of classification breaks down when asexuality arises more than once (creating homoplasy). For example, the asexual Candida glabrata is found within the Saccharomyces clade when molecular phylogenetics is applied. The problem lies in that many of these species appear very similar visually and microscopically and so there had not been enough phylogenetically informative phenotypic characters to easily classify them further. With the use of molecular phylogenetics the classifications have been improved as shown in several studies, however we retain the historical nature of the genus and species names for these organisms for the time being even though the phylogenetic diversity of species in the “genus” is much broader than other genus-level classifications. It will be interesting to see whether taxonomic proposals like PhyloCode or traditional revisions of the species names will provide new names for the group.

The Candida Genome Database (CGD) sister to the Saccharomyces Genome Database (SGD) provides resources for phenotype and sequences related to human commensal and dimorphic fungus Candida albicans. A recent paper by Arnaud et al describes the resources that are available through their website. An essentially completed C. albicans diploid genome with curated gene models and annotations provides an essential resource for this model pathogenic system. In addition to the SC5314 strain of C. albicans the white-opaque (WO) strain can switch between different colony morphologies – white and smooth or gray and rod shaped.

6 additional species have had their genomes in the Candida clade have had their genomes sequenced including Pichia stipis, Debaryomyces hansenii, Candida lusitaniae, Candida tropicalis, Candida guilliermondii, and Lodderomyces elongisporus. These resources will hopefully shed some light on the importance and mechanisms for dimorphic switching in the pathogen C. albicans, the importance and evolution of alternative codon usage in the clade, and better usage of the industrial yeasts like P. stipitis and D. hansenii.