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Focused discussion on fungal ecology and evolution especially fungal disease and human-fungal interactions.

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  • May 24, 2013
  • 07:57 AM
  • 62 views

Could you fill a beaker with the fungi in your body?

by Fungi in Bath Fungal Research

--> The mycobiome is starting to get a little traction!When will we know the weight of the fungi on and in our bodies? The human microbiota has been recognized as hugely important in the last few years, but that has almost entirely focused on bacteria. I’ve been interested in the mycobiome of the human built environment for a while, and I certainly haven’t been alone. People tend to think of fungi as a problem in buildings, on or in plants, and in the outside air. However, there is still so much unknown about the mycobiota of animals including humans. Only last year, there was a key discovery about mammal-fungal interactions in the gut that may drive some rather sever disease  in humans (ulcerative colitis)*, and it appears things are starting to pick up pace for the mycobiome, largely with the help of sequencing technology.Using over 5 million sequences of a standard fungal ID rDNA fragment, Findley et al. show specific fungal communities on human skin that shift with location on the body while bacteria shift depending on the site physiology. They also found startling fungal commensal diversity on the skin. Most of the identification they did was only to genus level, but for the predominant fungal genus, Malassezia, they identified species. Unlike Candida, which I think is basically a single species of human commensal out of a diverse group of environmental Saccharomycetales yeasts, Findley et al. found 11 of the 14 described species of Malassezia species consistently on the body. More interestingly it was mostly in the distribution of these species that the structure of the fungal community over the core body emerged. Different core body locations were dominated by different Malassezia species. The feet were another thing altogether. The fungal community on feet was vastly different from the core body and much more diverse. The fungal communities also differed from each other depending on site on the foot (toe nail, toe web, heel), but only really in feet showing clinical signs of infection (skin flaking etc.).They also found a kind of outlier individual who had a short course of treatment oral antifungal treatment months previous to the study. This individual had vastly different fungal community composition than the others but the bacterial community was not different.Having seen this I wonder how much abundance plays a role. Sometimes when abundance is high communities are less diverse. I think there could be parallels in other kinds of mycobiomes for what they’ve found on humans. Another clear thing to think about is the long-term effect on fungal communities of application of antifungals/fungicides. It’s exciting to see this level of detail in a study, but obviously, with only ten people studied, the Findley et al. work is small scale and a lot more patterns could emerge with new studies. Let’s get sequencing the Tube fungal community!*As an aside, I have often wondered how much the amphibian disease community cares about the immune response effects of Basidiobolus on amphibians infected with Batrachochytrium.  Iliev, I., Funari, V., Taylor, K., Nguyen, Q., Reyes, C., Strom, S., Brown, J., Becker, C., Fleshner, P., Dubinsky, M., Rotter, J., Wang, H., McGovern, D., Brown, G., & Underhill, D. (2012). Interactions Between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis Science, 336 (6086), 1314-1317 DOI: 10.1126/science.1221789Findley, K., Oh, J., Yang, J., Conlan, S., Deming, C., Meyer, J., Schoenfeld, D., Nomicos, E., Park, M., Becker, J., Benjamin, B., Blakesley, R., Bouffard, G., Brooks, S., Coleman, H., Dekhtyar, M., Gregory, M., Guan, X.,... Read more »

Iliev, I., Funari, V., Taylor, K., Nguyen, Q., Reyes, C., Strom, S., Brown, J., Becker, C., Fleshner, P., Dubinsky, M.... (2012) Interactions Between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis. Science, 336(6086), 1314-1317. DOI: 10.1126/science.1221789  

Findley, K., Oh, J., Yang, J., Conlan, S., Deming, C., Meyer, J., Schoenfeld, D., Nomicos, E., Park, M., Becker, J.... (2013) Topographic diversity of fungal and bacterial communities in human skin. Nature. DOI: 10.1038/nature12171  

  • May 24, 2013
  • 02:00 AM
  • 68 views

Nonessential heat shock proteins affect Candida albicans virulence

by Fungi in Bath Fungal Research

Picking up on my infatuation with all things Hsp, today more on the effects of two of the large Hsps on Candida albicans biofilm formation and virulence in mice and worms.Ssa1, a member of the Hsp70 family, is traditionally implicated in protein folding and entwining. Following heat shock, Ssa1 expression increases, which is a hallmark of heat shock proteins. Recently, Ssa1’s role in Candida albicans’ virulence has been extensively characterized. A series of experiments involving C. albicans mutant strains demonstrated that deletion of SSA1 (i) has no effect on survival in the mouse model of candidiasis of the bloodstream, (ii) leads to reduced fungal burden in mouse organs, (iii) results in significantly smaller lesions on the tongues of infected mice, (iv) yields less damage to endothelial and epithelial cells, and (v) causes less endocytosis. These effects are due to Ssa1 localizing to the outermost part of the cell wall where it governs binding to cadherins. Thus, lack of Ssa1 results in poor adherence, endocytosis and invasion, all of which are determinants of virulence in C. albicans. Interestingly though, filaments of SSA1 deletion strains are of comparable length to those of wild type cells.On the note of Hsp redundancy, Ssa1 has a paralog, a second copy in the genome so to speak, which is 98% identical. Yet, SSA2deletion mutants resemble the wild type. This is probably due to increased SSA1 expression levels that compensate for the lack of SSA2. Though, why then does SSA2 not make up for SSA1 deletion?Hsp104also entwines damaged proteins and cooperates with Ssa1 in refolding and reactivating them. Its expression is not just induced in response to heat but several other stresses, such as ethanol and arsenite, highlighting its role as a general anti-stress chaperone. Fungal virulence is contingent on stress responses thus suggesting a role for this chaperone in virulence, which was characterized most recently by studying the effect of HSP104deletion on survival of heat shock, biofilm formation, a critical virulence trait, and killing of worms, an invertebrate model host. Not too surprising, Hsp104 is required for thermotolerance, biofilm formation and structure as well as virulence in the worm model. Furthermore, Hsp104 appears to be haploinsufficient, which means that the phenotype of the HSP104/hsp104 is intermediate between the wild type and the null.Curiously, expression of Hsp70/Ssa1, Hsp90, and Hsp104 is induced by the one and only Hsf1.... Read more »

  • May 17, 2013
  • 03:59 AM
  • 26 views

Heat Shock Proteins Hone Candida albicans Drug Resistance

by Fungi in Bath Fungal Research

@font-face { font-family: "Cambria"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0cm 0cm 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; } Based on their molecular weight, heat shock proteins (Hsps) are grouped into five families Hsp100, Hsp90, Hsp70, Hsp60 and small Hsps. As their name implies, they play a critical role during heat stress, upon which they will refold denatured proteins. This way cells experiencing higher than normal temperatures protect themselves from the consequences of protein aggregation and denaturation, which could be dramatic as anyone who has ever boiled an egg knows.A few years ago, Hsp90 was shown to potentiate the evolution of antifungal drug resistance through its client protein calcineurin, a phosphatase that orchestrates fungal responses to environmental stimuli.As it turns out, Hsp90 is not the only Hsp modulating Candida albicans drug resistance. Recently, two studies demonstrated that Hsp21 and Msi3, an Hsp70 family member, affect antifungal drug resistance as well. Hsp21 is a small oligomeric Hsp that suppresses unfolded protein aggregation upon heat stress in diverse plants. In Candida albicans deletion of Hsp21 results in sensitivity to drugs targeting the cell membrane and the cell wall as well as calcineurin, which is reminiscent of Hsp90. Unlike Hsp90, Hsp21 is not essential and more importantly does not appear to have a human homolog. Thus, Hsp21 has the potential to yield a promising drug target. Amongst the larger Hsps, the Hsp70 family member Msi3 plays a role in resistance to antifungal drugs as well. Like Hsp90, Msi3 is essential and has a human homolog (Hsp110). Amino acid sequence identify though is substantially lower (37%) than between the Candidaand the human Hsp90 homolog (61%).Thus, Hsps are more than one-trick-ponies. At least three Hsps affect antifungal drug resistance in part through calcineurin, which is a verified Hsp90 client. It remains to be determined if Hsp21 and Msi3 stabilize and activate calcineurin as well and if all three potentially act in concert and are thus non-redundant with regard to antifungal drug resistance. Next time more about how Hsps shape Candida virulence traits.Cowen, L. (2005). Hsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi Science, 309 (5744), 2185-2189 DOI: 10.1126/science.1118370 Mayer, F., Wilson, D., & Hube, B. (2013). Hsp21 Potentiates Antifungal Drug Tolerance in Candida albicans PLoS ONE, 8 (3) DOI: 10.1371/journal.pone.0060417 Nagao, J., Cho, T., Uno, J., Ueno, K., Imayoshi, R., Nakayama, H., Chibana, H., & Kaminishi, H. (2012). Candida albicans Msi3p, a homolog of the Saccharomyces cerevisiae Sse1p of the Hsp70 family, is involved in cell growth and fluconazole tolerance FEMS Yeast Research, 12 (6), 728-737 DOI: 10.1111/j.1567-1364.2012.00822.x... Read more »

  • August 29, 2012
  • 06:20 AM
  • 305 views

More Basidiobolus Emergence?

by Fungi in Bath Fungal Research

Basidiobolus (the fungus that pictured on the background image of this blog) still seems to be gaining steam as a possibly emerging and/or frequently mis- or undiagnosed pathogen in incompetent humans (see my previous hacky post about this). In another paper out in the Journal of Medical Microbiology, Geramizadeh et al. report 14 more cases over the last decade in southern Iran (Fars province). Although only a single case is reported with positive culture identification, the other cases were presumed Basidiobolus based on histology. Two of the patients (infants) died, but the others were alive after surgery, and post operative anti-fungal treatments (one patient had a relapse or re-infection). These doctors did not use the saturated KI (the drug of choice in some Indian Basidiobolus literature).In some of our previous work we showed that parts of the Basidiobolus genome differed in copy number and the genome was fairly large for a fungus, but we have also found that Basidiobolus had a temperature dependent phenotype. When temperatures got near mammalian body normal (33º-38º), the fungus switched to a yeast-like growth form. From the histology sections in case reports, infectious Basidiobolus was growing as filamentous hyphae. Perhaps this fungus has a longer history of mammalian gut colonization than has been recognized? I think it is looking like a good target to study phenotype switches, host-interaction, and genome instability. I'll try to write a short primer on Basidiobolus this week and publish here on London Fungal Research.Bita Geramizadeh, Razieh Foroughi, Marzieh Keshtkarjahromi, Seyedali Malekhosseini, & Abdolvahab Alborzi (2012). Gastrointestinal basidiobolomycosis, an emerging infection in immunocompetent host: a report of 14 patients Journal of Medical Microbiology DOI: 10.1099/jmm.0.046839-0... Read more »

Bita Geramizadeh, Razieh Foroughi, Marzieh Keshtkarjahromi, Seyedali Malekhosseini, & Abdolvahab Alborzi. (2012) Gastrointestinal basidiobolomycosis, an emerging infection in immunocompetent host: a report of 14 patients . Journal of Medical Microbiology. DOI: 10.1099/jmm.0.046839-0  

  • August 28, 2012
  • 11:30 AM
  • 251 views

Evolving by copy number variation and chromosomal copy number variation

by Fungi in Bath Fungal Research

In Cryptococcus neoformans var. grubii (Cng) copy number variation (CNV) is happening on at least two levels. On one hand Chow et al. show not only that there natural polymorphism in copy number in a tandem repeat of a gene (ARR3), but that copy number can be selected for via arsenite. ARR3, the arsenite efflux transporter gene they found was located in the subtelomeric region of Chromosome 3, and subtelomeric regions are thought to undergo structural variation at a higher rate than other parts of the genome. However, Cng also shows evidence rapid adaptive aneuploidy or chromosomal copy number variation (CCNV). I have yet to see an estimate of these rates of CNV or CCNV in Cng populations. Does the presence of CCNV promote CNV or vice versa in Cng? Chow et al. show that the arsenite CNV example does not effect virulence, but most of the CCNV work suggests some strong effects on azole resistance which in turn effects patient outcome. These are clearly evolutionary mechanisms that fungal evolutionary biologists should try to understand better.Eve W. L. Chow, Carl A. Morrow, Julianne T. Djordjevic, Ian A. Wood, & James A. Fraser (2012). Microevolution of Cryptococcus neoformans Driven by Massive Tandem Gene Amplification Molecular Biology and Evolution DOI: 10.1093/molbev/mss066... Read more »

Eve W. L. Chow, Carl A. Morrow, Julianne T. Djordjevic, Ian A. Wood, & James A. Fraser. (2012) Microevolution of Cryptococcus neoformans Driven by Massive Tandem Gene Amplification . Molecular Biology and Evolution. DOI: 10.1093/molbev/mss066  

  • August 27, 2012
  • 08:44 AM
  • 432 views

The Rise of Fungi: The Demise of Dinosaurs

by Fungi in Bath Fungal Research

The demise of the dinosaur and reptile dominance at the K-T boundary has been the subject of so much speculation, that it can be hard to filter out the rampant storytelling from the underlying observations. In a fairly recent Pearl piece in PLoS Pathogens, Arturo Casadevall summarizes and advances his idea for a fungal role in the rise of mammals and the end of reptilian dominance.Many of the key bits in the argument focus on mammalian resistance to fungal infection due to endothermy and the interaction between body temperature and vertebrate immunity. Warmer body temperatures can exclude many fungi, and optimal body temperature is a key regulator of successful immune response. Large-bodied warm blooded dinosaurs would have depended on high food intake to maintain body temperatures, and the disruption of the ecosystem, including the near complete lack of phtosynthesis, would have limited their ability to mount successful defences against disease. Meanwhile, fungi could take advantage of the saprophytic paradise created by the bloom of available dead plant material. Such a bounce in fungal biomass could have produced conditions favouring disease outcomes for animals that would have normally resisted lower fungal doses with relatively more effective immune responses.This is an interesting theory, particularly given the huge numbers and diversity of invisible fungal propagules that are regularly encountered in the air, and the recent emergence of fungal and fungal-like diseases threatening animals with extirpation and extinction. However, I wonder how much fungi mattered as a selective force compared the to other factors at the time. Would body size and food inflexibility have been a bigger more influential filter? Something Casadevall did not discuss much was the relative success of smaller-bodied adaptable reptiles (Squamates) or the amphibians across the Tertiary, although amphibians are now under serious threat of a fungal disease driven mass extinction. I also wondered why Casadevall didn't explore fungal adaptation during the period of mass upheaval near the K-T boundary. Fungi are certainly not universally saprotrophs. What are the limits and influences on fungal diversity. Was there a fungal crash or expansion at the K-T boundary? Obviously, another good Pearl since not only have I learned about the core about this particular theory, but I have had my curiosity piqued enough to start digging into diversification literature I have not scoured in years.As will now be normal for these posts until further notice, Research Blogging citations will be proceeded with the icon, but links to other works may be embedded in the text of the post. Arturo Casadevall (2012). Fungi and the Rise of Mammals PLoS Pathogens DOI: 10.1371/journal.ppat.1002808... Read more »

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