A 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”
There 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
Ignazio Carbone and colleagues published a recent analysis of the evolution of the aflatoxin gene cluster in five Aspergillus fungi entitled “Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster” in BMC Evolutionary Biology. The authors were able to identify seven modules pairs of genes whose history of duplication were highly correlated. Several genomes of Aspergillus have been sequenced along with more Eurotioales fungi. Continue reading Evolution of aflatoxin gene cluster
A 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.
The genome of the wheat and cereal pathogen Fusarium graminearum was published in Science this week in an article entitled “The Fusarium graminearum Genome Reveals a Link Between Localized Polymorphism and Pathogen Specializationtion”. The project was a collaboration of many different Fusarium research groups. The genome sequencing was spearheaded by the Broad Institute at Harvard and MIT and is part of a larger project to sequence several different species of Fusarium. The group sequenced a second strain in order to identify polymorphisms.
Some of the key findings
- The presence of Repeat Induced point-mutation (RIP) has likely limited the amount of repetitive and duplicated sequences in the genome
- Most of the genes unique to F. graminearum (and thus not present in 4 other Fusarium spp genomes) are found in the telomeres
- Between the sequenced strains SNP density ranged from 0 to 17.5 polymorphisms per kb.
- Some of the genes expressed uniquely during plant infection (408 total) include known virulence factors and many plant cell-wall degrading enzymes.
- The genes showing some of the highest SNP diversity tended to be unique to Fusarium and often unique to F. graminearum
Aspergillus fumigatus can be dangerous, even to those with intact immune systems. A recent article in Discover magazine’s Vital Signs describes how dangerous the ubiquitous fungus can be.
Several more fungi are on the docket for sequencing at JGI through their community sequencing program. This includes
This complements an ever growing list of fungal genome sequences which is probably topping 80+ now not including the several dozen strains of Saccharomyces that are being sequenced at Sanger Centre and a separately funded NIH project to be sequenced at WashU.
A recent paper I found interesting (and I am sure was interesting to Dr Logsdon) about Multiple losses of sex within a single genus of Microsporidia. In the paper Joseph Ironside describes multiple instances of loss of sex within the Nosema/Vairimorpha group testing the hypothesis that the ancestral lineage was asexual. The group of species are undergoing rapid evolution where changes in lifestyle/lifecycle can occur even among very closely related lineages. In order to do test a formal hypothesis about whether the ancestor was asexual or sexual this the author had to improve the resolution of the phylogenetic relationships of these species and deal with some technical problems due to mutational biases in the rDNA sequences. The result he found was that the ancestral lineage was sexual and that asexuality arose multiple times among these species. He also provides a caution:
“The rapid evolution of microsporidian life cycles indicated by this study also suggests that even closely related microsporidia cannot be assumed to have similar life cycles and the life cycle of each newly discovered species must therefore be completely described.”
Something one has to be careful about in comparative studies of these species.
Continue reading Multiple Losses of sex within Microsporidia
A while back, Jason blogged briefly on a New Scientists article about the rise of a new Puccinia graminis strain, Ug99, that is spreading through West African wheat fields at an enormous rates. It looks like this story is growing in the scientific conciousness, as Science is now running an article on the spread of this wheat pandemic.
The article has a nice bit of background regarding the rise of the disease. It seems that it is spreading so quickly for due to its relatively broad host range compared to other strains. While scientists have been working to derive resistant wheat varieties, Puccinia has successfully foiled their recent attempts by mutating to acheive resistance to the plant expressed Sr24.
To boot, this strain has been found in Yemen, allowing its spores to hitch a ride along the winds that blow north along the Indian Ocean, putting much of the global bread basket at risk (I imagine that the last thing the middle east needs right now is a wheat shortage). The last time a rust spread through this area, it caused 1 billion dollars in damage. Given the extensive host range of this variety, experts predict that damages will exceede at least three times this amount.
Fortunately, researchers in Ethiopian have derived two wheat strains that may be resistant to Ug99. However, it can take several years to get these wheat strains in the ground and, ultimately, no one is certain that Ug99 won’t cleverly find a way to adapt resistance. We should keep our ears to the rail on this one: it could be a big problem.
The New Scientist has an article about the spread of black stem rust caused by Puccinia graminis. We briefly mentioned the 1st release of a Puccinia genome in January. Some more links about the spread of the Ug99 virulent strain.
Continue reading Puccinia black stem rust disease spreading
I’ve never worked with Magnaporthe grisea, the fungus responsible for rice blast, one of the most devastating crop diseases, but I do know that its life cycle is complicated and that knocking out roughly 61% of the genes in the genome and evaluating the mutant phenotype to infer gene function is not trivial. In their recent letter to Nature, Jeon et al did what many of us have dreamed of doing in our fungus of interest: manipulate every gene to find those that contribute to a phenotype of interest.
In their study, the authors looked for pathogenecity genes. Interestingly, the defects in appressorium formation and condiation had the strongest correlation with defects pathogenicity, suggesting that these two developmental stages are crucial for virulence. Ultimately, the authors identify 203 loci involved in pathogenecity, the majority of which have no homologous hits in the sequence databases and have no clear enriched GO functions. Impressively, this constitutes the largest, unbiased list of pathogenecity genes identified for a single species (though so of us, I’m sure, may have a problem with the term “unbiased”).
If you’d like to play with their data, the authors have made it available in their ATMT Database.