Category Archives: animal pathogen

Recent animal-associated fungal genome papers

The genomes of five dermatophyte fungi were sequenced and the analyses of their lifestyles presented in a new paper out in mBio in Martinez et al. 2012. The authors were able to identify gene family changes that associate with lifestyle changes including proteases that can degrade keratin suggesting how these species have adapted to obtaining nutrients from an animal host. The continued finding of fungal-specific kinase families in these fungi, extending the observations from previous studies in Coprinopsis and Paracoccidioides on the FunK1 kinase family, makes me hope we will some day get some molecular information on the specificity of these families in addition to these copy number observations.
Another paper published in Genome Research this summer from Emily Troemel‘s lab and the Broad Institute describes the sequencing of two microsporidia species that are natural parasites of Caenorhabditis.The paper reveals some suprising things about Microsporidia evolution including the presence of a clade-specific nucleoside H+ symporter which is only found in bacteria and some eukaryotes and not in any Fungi. The phyletic distribution suggested it was acquired more recently and couple from lateral gene transfer. This acquisition likely helps the microsporidia cells obtain nucleosides from the host since the parasite cannot synthesize these. There is also evidence of evolution of microsporidia-specific secretion signals in the hexokinases which may be a mechanism for delivery of these enzymes into host cells to catalyze rapid growth once inside the host. Many more gems in this paper including phylogenetic placement of the microsporidia from phylogenomic approaches (also see related recent work from Toni Gabaldon‘s lab).

Few fungi+host papers

Three papers on some cool fungi that interact with hosts and I recommend them for a good read.

One is coverage of by Ed Yong on rice blast (Magnaporthae orzyae) on paper from Nick Talbot and Gero Steinberg‘s lab on appressorium development in Science this week.

A paper from my lab on role of an expansion of copy number of a chitin-binding domain in the amphibian pathogen B. dendrobatidis.

New Scientist also provides a nice summary of tripartite symbiosis paper on Metarhizium, insects, and plants from Mike Bidochka’s lab.

Microsporidia genomes on the way

New genomes from Microsporidia are on the way from the Broad Institute and other groups, and will be a boon to those working on these fascinating creatures. Microsporidia are obligate intracellular parasites of eukaryotic cells and many can cause serious disease in humans. Some parasitize worms and insects too. The evolutionary placement of these species in the fungi is still debated with recent evidence placing them as derived members of the Mucormycotina based on shared synteny (conserved gene order), in particular around the mating type locus.  There is still some debate as to where this group belongs in the Fungal kingdom, with their highly derived characteristics and long branches they are still make them hard to place.  The synteny-based evidence was another way to find a phylogenetic placement for them but it would be helpful to have additional support in the form of additional shared derived characteristics that group Mucormycotina and Microsporidia. There is hope that increased number of genome sequences and phylogenomic approaches can help resolve the placement and more further understand the evolution of the group.

For data analysis, a new genome database for comparing these genomes is online called MicrosporidiaDB. This project has begun incorporating the available genomes and providing a data mining interface that extends from the EuPathDB project.

Dynamics of amphibian pathogen infection cycles
Two papers out this week on the population dynamics and epidemiology of the chytrid pathogen of amphibians, Batrachochytrium dendrobatidis (Bd). This is work from the Vredenburg and Briggs labs that includes several decade-long studies of frog declines and the prevalence of Bd.

See Vance in action swabbing a frog

In the Briggs et al paper, they describe a 5-year study on the fungal load in surviving populations of frogs in Sierra Nevada mountain lakes.  They find that adult frogs that have low enough fungal load escape chytridiomycosis and can actually lose and regain infection. They propose that fungal load dynamics are the reason behind differential survival of various populations of mountain frogs. They conclude that:

“Importantly, model results suggest that host persistence versus extinction does not require differences in host susceptibility, pathogen virulence, or environmental conditions, and may be just epidemic and endemic population dynamics of the same host–pathogen system.”

So they propose that differences in the populations that are coming down with the disease is due only to “density-dependent host–pathogen dynamics” not that some populations are resistant. They go on to provide a detailed model of persistence if the host and pathogen, chance of reinfection, and survival of the host which is derived from the long-term study data.  There are many more interesting findings and models proposed in the paper. It also further reinforces (for me) the need to know more about the molecular basis of the host-pathogen interactions and more about how the fungus persists without a host, lifestyle of how it overwinters, and the details of the microbe-host interactions, and the infection dynamic when zoospores disperse from infected frogs.

The Vrendenburg et al paper adresses the dynamics of population decline in the mountain yellow-legged frogs over a periods of 1-5 and 9-13 year study in 3 different study sites at different sampling intervals.  The authors were able to catalog the species decline and conduct skin swabbing to assess Bd prevalence. They found that the fungus spread quickly as it could detected in virtually all the lakes over the course of a year starting with a 2004 survey. The dramatic declines of frog populations in these lakes followed in the years subsequent to the initial detection. This sadly predicts that most if not all of the mountain lakes will go extinct for the frogs as the current tadpoles develop into frogs in the next 3 years and then fall victim to Bd. Based on their sampling work, the authors were also able to correlate what fungal burden predicted a subsequent decline – in populations where more the ~10,000 zoospores were detected in a swab from frog skin, then the frog population was about to experience a sharp decline.  The take-home from this work is that finding ways to keep the intensity of fungal infections down could provide a meaningful intervention that could prolong the viability of the population.

Briggs, C., Knapp, R., & Vredenburg, V. (2010). Enzootic and epizootic dynamics of the chytrid fungal pathogen of amphibians Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0912886107

Vredenburg, V., Knapp, R., Tunstall, T., & Briggs, C. (2010). Dynamics of an emerging disease drive large-scale amphibian population extinctions Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0914111107

Origins and evolution of pathogens An article in PLoS Pathogens by Morris et al describe a hypothesis about the evolution and origins of plant pathogens applying the parallel theories to the emergence of medically relevant pathogens. The authors highlight the importance of understanding the evolution of organisms in the context of emerging pathogens like Puccinia Ug99 for our ability to design strategies to protect human health and food supplies.  Both bacterial and fungal pathogens of plants are discussed but I (perhaps unsurprisingly) focus on the fungi here. Continue reading Origins and evolution of pathogens

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)

Bat White-nose syndrome brevia

A Brevia piece in Science today describes efforts to describe the causal agent in white-nose syndrome (WNS) in bats which appears to be contributing to bat decline. According to the authors, previous work had described an uncharacterized fungus associated with bats that showed signs of being sick with WNS. This is an emerging pathogen as the samples described in this paper were from Spring 2008. Phylogenetic analysis of the rDNA (and presumably ITS) sequence of fungal isolates from diseased bats placed it as a Geomyces spp, in the Helotiales order (in the Leotiomycetes if you are wondering what are the closest sequenced fungal genomes for this species). Other Geomyces spp are also psychrophiles and found colonizing the skin of animals in cold climates (it must be hard to make a living). The authors suggest the finding of this fungal species on bats is consistent with its involvement in disease. The authors also make the parallel to chytridiomycosis, an emerging pathogen of amphibians that is contributing to the worldwide amphibian decline.

This is just the first of hopefully several publications studying this phenomenon as this brief piece sets the stage for additional questions. It is not yet been shown that this fungus is actually causing the disease, i.e. satisfying Koch’s postulates, and isn’t just a canary in the coal mine. So-called opportunistic fungi like Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans cause infections that emerge after the patient’s immune system has been compromised by something else such as HIV or immunosuppressant drugs as part of an organ transplant regime. It is possible that the white-nose syndrome (ie white conidia from Geomyces sp is just a manifestation of an infection of a commensal organism like thrush or yeast infections of Candida albicans that only emerge when something else has knocked down the host’s immune system. I don’t know if this same Geomyces sp can be cultured from healthy bats from so-far uninfected colonies which would suggest the fungus is present all the time.

As we track and learn more about natural die-offs and disease in animals from infectious diseases there are series of recent fungal-associated disease of animal populations including honeybees perhaps from a virus and a microsporidium, frogs and amphibians via Batrachochytrium dendrobatidis, and white-nose syndrome. Diseases like Cryptococcus gattii are also examples of pathogens that may be able to infect healthy animals and humans. It seems quite important to know more important to track and study how these outbreaks spread and the evolutionary and ecological basis for the sudden rise in infection and mortality in animal populations to understand diseases of human relevance as well.

Related links:

D. S. Blehert, A. C. Hicks, M. Behr, C. U. Meteyer, B. M. Berlowski-Zier, E. L. Buckles, J. T. H. Coleman, S. R. Darling, A. Gargas, R. Niver, J. C. Okoniewski, R. J. Rudd, W. B. Stone (2008). Bat White-Nose Syndrome: An Emerging Fungal Pathogen? Science DOI: 10.1126/science.1163874