BBC News reports that Britain is running out of mycologists. There were 32 in the 1990s, but just eight now. Scientists say we should be worried as, without a British research base, other countries could stand to make lucrative fungi-based discoveries in everything from medicine to engineering.
Unbelievable as it sounds, leaf-cutter ants developed the secret of agriculture over 50 million years ago. In this article in Microbiology Today, Garret Suen and Cameron Currie describe how freshly-cut leaves are incorporated into gardens for the growth of a specialized fungus that the ants use for food:
Until about a decade and a half ago, research on fungus-growing ants focused primarily on the ants and their foraging behaviour. It wasn’t until the early 1990s that this focus shifted to the fungus gardens and their associated microbial communities. Since the ant gardens are maintained in soil chambers, they are routinely exposed to a number of potential pathogens that could infect and overtake a garden. In fact, many of the ant colonies do become overgrown by fungal pathogens, often resulting in the death of the colony. Intensive sampling of the fungal communities within the gardens revealed that a specialized microfungal pathogen selectively attacks the gardens of the fungus-growing ants.
Aspergillosis is a group of lung diseases caused by infection with Aspergillus, a fungus (mold) that grows on decaying plant matter. Because Aspergillus is widespread in the environment, people often breathe in its spores. For most people, this is not a problem – their immune system rapidly kills the fungal spores. However, people with asthma or cystic fibrosis sometimes develop allergic bronchopulmonary aspergillosis, a condition in which the spores trigger an allergic reaction in the lungs that causes coughing, wheezing. and breathlessness. Other people can develop an aspergilloma – a fungus ball that grows in cavities in the lung caused by other illnesses such as tuberculosis. However, the most serious form of aspergillosis is invasive aspergillosis. This pneumonia-like infection, which is fatal if left untreated, affects people who have a weakened immune system (for example, people with leukemia) and can spread from the lungs into the heart, brain, and other parts of the body. Aspergillosis is usually treated with triazole drugs, which inhibit an enzyme that the fungus needs to make its cell membranes; this enzyme is encoded by a gene called cyp51A. Voriconazole is the first-line therapy for aspergillosis but itraconazole and posaconazole are also sometimes used and ravuconazole is in clinical development.
About half of patients with invasive aspergillosis recover if they are given triazoles. Worryingly, however, strains of Aspergillus fumigatus (the type of Aspergillus usually involved in invasive aspergillosis) with resistance to several triazoles have recently been isolated from some patients in The Netherlands. If multi-azole resistant strains of A. fumigatus become common, they could have a serious impact on the management of invasive aspergillosis. However, noone knows what proportion of A. fumigatus strains isolated from patients with aspergillosis are resistant to several azole drugs. That is, no-one knows the “prevalence” of multi-azole resistance. In a new study, researchers investigated the prevalence and development of azole resistance in A. fumigatus.
Since 1994, all fungal isolates from patients at the Radboud University Nijmegen Medical Center in the Netherlands have been stored. The researchers’ search of this collection yielded 1,908 A. fumigatus isolates that had been collected from 1,219 patients over a 14-year period. Of these, the isolates from 32 patients grew in the presence of itraconazole. All the itraconazole-resistant isolates (which also had increased resistance to voriconazole, ravuconazole, and posaconazole) were collected after 1999; the annual prevalence of itraconazole-resistant isolates ranged from 1.7% to 6%. The researchers then sequenced the cyp51A gene in each resistant isolate. Thirty had a genetic alteration represented as TR/L98H. This “dominant resistance mechanism” consisted of a single amino acid change in the cyp51A gene and an alteration in the gene’s promoter region (the region that controls how much protein is made from a gene). The researchers also analyzed A. fumigatus isolates from patients admitted to 28 other hospitals in the Netherlands. Itraconazole resistance was present in isolates from 13 patients (out of 101 patients) from nine hospitals; the TR/L98H genetic alteration was present in 69% of the itraconazole-resistant isolates. Finally, itraconazole resistance was present in six isolates from four other countries (out of 317 isolates from six countries); only one Norwegian isolate had the TR/L98H genetic alteration.
These findings indicate that azole resistance is emerging in A. fumigatus and may already be more prevalent than generally thought. Given the dominance of the TR/L98H genetic alteration in the azole-resistant clinical isolates, the researchers suggest that A. fumigatus isolates harboring this alteration might be present and spreading in the environment rather than being selected for during azole treatment of patients. Why azole resistance should develop in A. fumigatus in the environment is unclear but might be caused by the use of azole-containing fungicides. Further studies are now urgently needed to find out if this is the case, to measure the international prevalence and spread of A. fumigatus isolates harboring the TR/L98H genetic alteration, and, most importantly, to develop alternative treatments for patients with azole-resistant aspergillosis.
Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. 2008 PLoS Med 5(11): e219
Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. We investigated the prevalence of itraconazole (ITZ) resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8%) from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. Azole resistance has emerged in A. fumigatus and might be more prevalent than currently acknowledged. The presence of a dominant resistance mechanism in clinical isolates suggests that isolates with this mechanism are spreading in our environment.
Chemists have discovered that fungi can naturally absorb microscopic metal particles into their flesh in a way that could see metallic fungus used as catalysts or disinfectants. Industrial catalysts often rely on processes that happen on the surface of metals, so nanoparticles of catalyst with large surface-area-to-volume ratios are particularly effective. But such particles are only effective if they are prevented from clumping together using a chemical solution, which makes it difficult to separate the catalyst from the products of a reaction. Some fungi can assimilate and stabilise nanoparticles as they grow. Because the nanoparticles are immobilised on fungal filaments, they can be easily recovered later.
Fungal Templates for Noble-Metal Nanoparticles and Their Application in Catalysis. 2008 Angewandte Chemie International 47: 7876-7879
The combination of living structures with advanced materials, for example, as realized in cell-semiconductor coupling, or by using small biological forms as templates for nanotechnological applications, is becoming the focus of more and more interest. Composite materials consisting of magnetic or semiconducting nanoparticles incorporated into bacterial superstructures have been synthesized. To date, the main work on nanoparticle biomaterial hybrid structures has been done using functionalized gold nanoparticles assembled onto bacteria. For example Berry et al. were able to synthesize highly electrically conducting materials by assembling lysine-coated gold nanoparticles onto Bacillus cereus. It has also been demonstrated that cetyltrimetylammonium bromide (CTAB) terminated gold nanoparticles of different shapes (for example, nanorods) can be assembled onto the surface of bacteria. Other techniques for controlled assembly of gold nanoparticles were performed by DNA-modification of the surface, using diatoms and fungi as templates. Very recently Sugunan et al. reported the growth of fungi directly in gold nanoparticle solutions, using sodium glutamate as the reducing agent. Nutrition-driven assembly of gold onto the fungal mycelia was detected. The resulting hybrid structure exhibited optical properties of bulk gold and an electric resistivity close to that of the respective bulk solid.
In this article we show the ability of a variety of fungi to grow in citrate-stabilized colloidal medium and test their affinity for different noble-metal nanoparticles. Fungal growth takes place directly in the as-prepared gold, silver, platinum, and palladium nanoparticle solutions. Decoration of the fungal surface takes place without any further functionalization. The resulting hybrid systems have outer dimensions of about 0.1 cm3 and optical properties similar to the respective nanoparticle solutions. Differences in the metal affinities with respect to the morphology were observed by scanning electron microscopy. The specific surface area of the systems obtained has been assessed. A fungus-platinum hybrid system was shown to catalyze the redox reaction of hexacayanoferrate(III) and thiosulfate ions in aqueous solution. Dehydration of the metal-fungus hybrids was performed by critical point drying, thus conserving the three-dimensional macroscopic and microscopic shapes.
Besides the potential for applications in heterogeneous catalysis, other applications for these hybrid structures can also be considered. Silver or gold structures could be used as templates for surface-enhanced Raman spectroscopy and might also serve for fungi identification. Fungi decorated with silver could serve as disinfecting objects because of their high porosity and the well-known disinfection capability of silver. Besides electronic or sensoric applications, the effect described could be a useful tool for biochemical investigations, for example concerning the fungal heavy-metal-accumulation effect or for detecting differences in surface modifications (for example, between spores and hyphae).
Ale, fermented using the yeast Saccharomyces cerevisiae, has been brewed since ancient times, possibly as early as 6000 BC. In contrast, lager beer, with its hallmark low-temperature fermentation (5°C–14°C), is a more recently developed alcoholic beverage, arising in Bavaria near the end of the Middle Ages. Lager gained worldwide popularity from the late 1800s with the advent of refrigeration, which allowed the necessary cool fermentation temperatures year-round. The lager yeast, Saccharomyces pastorianus, is distinct from S. cerevisiae in both physiological and genetic characteristics and is thought to have arisen in response to selective pressures from cold brewing temperatures. This selection may have taken place during successive rounds of cold-temperature fermentations resulting from a 16th century Bavarian law that prohibited brewing during summer months because of the inferior quality of summer-brewed beers. S. pastorianus has been shown to be a hybrid organism, and it is likely that lager yeast arose by “instantaneous speciation” due to an interspecific hybridization event between Saccharomyces cerevisiae and Saccharomyces bayanus that occurred during these selective growth conditions.
By examining the genome of S. pastorianus, a recently-published paper shows that the hybridization between yeast species which gave rise to lager yeasts happened independently at least twice, not once as previously thought, giving rise to two broad families of lager beer, Group 1 yeasts used to brew “Saaz”-type beers such as Pilsner and Budweiser, and Group 2 yeasts used to brew “Frohberg” lagers such as Orangeboom and Heineken. Both groups contain multiple copies of genes beneficial to brewing, such as those that ferment maltose. Likewise, genes that adversely affect the process have been lost.
This work paves the way for characterization of specific genetic features of each strain that could aid in the brewing process, and could lead to new insights on how to directly control flavor and aroma in beer.
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Reconstruction of the genome origins and evolution of the hybrid lager yeast Saccharomyces pastorianus. Genome Research, September 11, 2008
Inter-specific hybridization leading to abrupt speciation is a well-known, common mechanism in angiosperm evolution; only recently, however, have similar hybridization and speciation mechanisms been documented to occur frequently among the closely related group of sensu stricto Saccharomyces yeasts. The economically important lager beer yeast Saccharomyces pastorianus is such a hybrid, formed by the union of Saccharomyces cerevisiae and Saccharomyces bayanus-related yeasts; efforts to understand its complex genome, searching for both biological and brewing-related insights, have been underway since its hybrid nature was first discovered. It had been generally thought that a single hybridization event resulted in a unique S. pastorianus species, but it has been recently postulated that there have been two or more hybridization events. Here, we show that there may have been two independent origins of S. pastorianus strains, and that each independent group – defined by characteristic genome rearrangements, copy number variations, ploidy differences, and DNA sequence polymorphisms – is correlated with specific breweries and/or geographic locations. Finally, by reconstructing common ancestral genomes via array-CGH data analysis and by comparing representative DNA sequences of the S. pastorianus strains with those of many different S. cerevisiae isolates, we have determined that the most likely S. cerevisiae ancestral parent for each of the independent S. pastorianus groups was an ale yeast, with different, but closely related ale strains contributing to each group’s parentage.
Montage of high-speed video clips showing sporangiophore discharge in the fungus Pilobolus kleinii. The videos were obtained at camera frame rates of up to 250,000 fps. Each discharge is completed in less than 0.25 milliseconds; an eye blink takes 100 milliseconds, or 400 times longer! The music is Verdi’s Anvil Chorus. Credit: Yafetto et al
Microscopic coprophilous (dung-loving) fungi help make our planet habitable by degrading the billions of tons of faeces produced by herbivores. But the fungi have a problem: survival depends upon the consumption of their spores by herbivores and few animals will graze on grass next to their own dung. Evolution has overcome this obstacle by producing an array of mechanisms of spore discharge whose elegance transforms a cow pie into a circus of microscopic catapults, trampolines, and squirt guns. A new paper examines the operation of squirt guns that fire spores over distances of more than 2 metres. The researchers used high speed cameras running at up to 250,000 frames per second to capture these blisteringly fast movements. Spores are launched at maximum speeds of 25 meters per second impressive for a microscopic cell corresponding to accelerations of 180,000 g. In terms of acceleration, these are the fastest flights in nature. The paper is significant for a number of reasons. This is the first study utilizing ultra-high-speed video cameras to capture the events of spore discharge in ascomycete and zygomycete fungi. Previous investigators relied upon models to predict ballistic parameters and produced erroneous estimates of velocities and accelerations. These estimates were then used to suggest that pressures within the spore guns were very high. Fungal cells generate pressure by osmosis and the authors used a combination of spectroscopic methods to identify the chemical compounds responsible for driving water influx into the guns. These experiments showed that the discharge mechanisms in fungi are powered by the same levels of pressure that are characteristic of the cells that make up the feeding colonies of fungi. Therefore, the long flights enjoyed by spores result not from unusually high pressure, but from the way in which explosive pressure loss is linked to the propulsion of the spores. There are similarities between the escape of the spores and the expulsion of ink droplets through nozzles on inkjet printers. Another important aspect of the new work is the way that it has allowed the researchers to test different models for the effect of viscous drag on microscopic particles and identify limitations in previous approaches to modeling. This information is very important for future biophysical studies on spore and pollen movement, which have implications for the fields of plant disease control, terrestrial ecology, indoor air quality, atmospheric sciences, veterinary medicine, and biomimetics.
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The Fastest Flights in Nature: High-Speed Spore Discharge Mechanisms among Fungi. 2008 PLoS ONE 3(9): e3237
Background: A variety of spore discharge processes have evolved among the fungi. Those with the longest ranges are powered by hydrostatic pressure and include “squirt guns” that are most common in the Ascomycota and Zygomycota. In these fungi, fluid-filled stalks that support single spores or spore-filled sporangia, or cells called asci that contain multiple spores, are pressurized by osmosis. Because spores are discharged at such high speeds, most of the information on launch processes from previous studies has been inferred from mathematical models and is subject to a number of errors.
Methodology/Principal Findings: In this study, we have used ultra-high-speed video cameras running at maximum frame rates of 250,000 fps to analyze the entire launch process in four species of fungi that grow on the dung of herbivores. For the first time we have direct measurements of launch speeds and empirical estimates of acceleration in these fungi. Launch speeds ranged from 2 to 25 meters per second and corresponding accelerations of 20,000 to 180,000 g propelled spores over distances of up to 2.5 meters. In addition, quantitative spectroscopic methods were used to identify the organic and inorganic osmolytes responsible for generating the turgor pressures that drive spore discharge.
Conclusions/Significance: The new video data allowed us to test different models for the effect of viscous drag and identify errors in the previous approaches to modeling spore motion. The spectroscopic data show that high speed spore discharge mechanisms in fungi are powered by the same levels of turgor pressure that are characteristic of fungal hyphae and do not require any special mechanisms of osmolyte accumulation.
Reduction of food intake, commonly referred to as dietary restriction, has been shown to slow ageing and extend lifespan in virtually every biological system examined. However, the underlying mechanisms that couple dietary restriction to lifespan extension remain poorly defined. Recently, the relatively simple eukaryote Saccharomyces cerevisiae (bakers’ yeast) has emerged as a powerful model system to study the genetic and physiological factors that alter lifespan. A recent paper shows that caffeine extends the lifespan of yeast.
This begs the question: can caffeine extend lifespan in humans? Caffeine is the most widely used psychoactive drug worldwide with coffee being the main source of caffeine in the Western diet. Tantalizingly, epidemiological studies have correlated habitual coffee consumption with a decreased relative risk of mortality. Drinking one cup of coffee results in an approximate peak plasma concentration of 1–10 μM caffeine in humans (with an estimated half-life of 2.5–4.5 h). Assuming that caffeine acts in a similar way in humans as in yeast, moderate coffee consumption compares well with the with the levels calculated to be necessary for lifespan extension in yeast, and thus provides mechanistic support for the correlative links between coffee consumption and longevity described above. At this concentration, caffeine does not appear to have deleterious consequences. Finally, caffeine has recently been shown to suppress cell transformation, suggesting that caffeine may also be a (well-tolerated) and effective anti-cancer agent.
Caffeine extends yeast lifespan by targeting TORC1. Molecular Microbiology 27 May 2008
Dietary nutrient limitation (dietary restriction) is known to increase lifespan in a variety of organisms. Although the molecular events that couple dietary restriction to increased lifespan are not clear, studies of the model eukaryote Saccharomyces cerevisiae have implicated several nutrient-sensitive kinases, including the target of rapamycin complex 1 (TORC1), Sch9, protein kinase A (PKA) and Rim15. We have recently demonstrated that TORC1 activates Sch9 by direct phosphorylation. We now show that Sch9 inhibits Rim15 also by direct phosphorylation. Treatment of yeast cells with the specific TORC1 inhibitor rapamycin or caffeine releases Rim15 from TORC1-Sch9-mediated inhibition and consequently increases lifespan. This kinase cascade appears to have been evolutionarily conserved, suggesting that caffeine may extend lifespan in other eukaryotes, including man.
Mitochondria have been found to also be the driver with regard to cell division, according to a group of biochemists who say this discovery could play a large role in finding cures for many human diseases. The scientists studied yeast cells and found that mitochondria, which generate 90 percent of the cell’s energy, can be the deciding factor behind how fast cells divide. The finding by Michael Polymenis and Mary Bryk and their research groups is published today in the open-access journal PLoS Genetics. The finding changes the traditional view of the mitochondrion from an “energy depot” at the service of its larger cellular host to a “command center” that directs cell division. The researchers used regular baker’s yeast (Saccharomyces cerevisiae) – commonly used in bread, wine and beer making – because many of the yeast cell’s processes are similar to those in human cells. From unicellular yeast to complex mammals, the process is the same. The job of a cell is to divide and grow. Metabolism takes in “food” and turns it into fuel and building blocks for DNA replication and gene expression. But when these processes falter, diseases can result. Too much cell division too quickly, for example, is typical of cancerous cells. Conversely, poor metabolism – stemming from mitochondrial deficiencies – is at the root of damage to various organs such as the brain, heart, skeletal muscles, and liver. All of the body processes that require a lot of energy are impacted by this, and at least 1 in every 4,000 people worldwide suffer from mitochondrial deficiencies that result in problems with normal development, motor control, vision, hearing, or liver and kidney function. Alternatively, there are times when speeding cell division might be useful as with wound healing and plant or crop production. If we can understand the basic pathway that regulates cell division, we can think of ways to tweak the different steps in that path with therapeutics to help people who have problems with these high-energy organs. The research showed that when a yeast cell’s mitochondria decided to “turn on the switch,” the cell’s nucleus, which carries most of the genetic material, received the message and cell division began. So now we need to connect that link. We need to understand how and when the mitochondria send the message. If we know how the message is sent, we might be able to control it.
Coordination between cellular metabolism and DNA replication determines when cells initiate division. It has been assumed that metabolism only plays a permissive role in cell division. While blocking metabolism arrests cell division, it is not known whether an up-regulation of metabolic reactions accelerates cell cycle transitions. Here, we show that increasing the amount of mitochondrial DNA accelerates overall cell proliferation and promotes nuclear DNA replication, in a nutrientdependent manner. The Sir2p NAD+-dependent de-acetylase antagonizes this mitochondrial role. We found that cells with increased mitochondrial DNA have reduced Sir2p levels bound at origins of DNA replication in the nucleus, accompanied with increased levels of K9, K14-acetylated histone H3 at those origins. Our results demonstrate an active role of mitochondrial processes in the control of cell division. They also suggest that cellular metabolism may impact on chromatin modifications to regulate the activity of origins of DNA replication. An Increase in Mitochondrial DNA Promotes Nuclear DNA Replication in Yeast. 2008 PLoS Genet 4(4): e1000047
