MicrobiologyBytes

The fungal kingdom is vast, spanning 1.5 to as many as 5 million species diverse as unicellular yeasts, filamentous fungi, mushrooms, lichens, and both plant and animal pathogens. The fungi are closely aligned with animals in one of the six to eight supergroups of eukaryotes, the opisthokonts. The animal and fungal kingdoms last shared a common ancestor 1 billion years ago, more recently than other groups of eukaryotes. As a consequence of their close evolutionary history and shared cellular machinery with metazoans, fungi are exceptional models for mammalian biology, but prove more difficult to treat in infected animals. The last common ancestor to the fungal/metazoan lineages is thought to have been unicellular, aquatic, and motile with a posterior flagellum, and certain extant species closely resemble this hypothesized ancestor. Species within the fungal kingdom were traditionally assigned to four phyla, including the basal fungi (Chytridiomycota, Zygomycota) and the more recently derived monophyletic lineage, the dikarya (Ascomycota, Basidiomycota). The fungal tree of life project has revealed that the basal lineages are polyphyletic, and thus there are as many as eight to ten fungal phyla. Fungi that infect vertebrates are found in all of the major lineages, and virulence arose multiple times independently. A sobering recent development involves the species Batrachochytrium dendrobatidis from the basal fungal phylum, the Chytridiomycota, which has emerged to cause global amphibian declines and extinctions. Genomics is revolutionizing our view of the fungal kingdom, and genome sequences for zygomycete pathogens (Rhizopus, Mucor), skin-associated fungi (dermatophytes, Malassezia), and the Candida pathogenic species clade promise to provide insights into the origins of virulence. Here we survey the diversity of fungal pathogens and illustrate key principles revealed by genomics involving sexual reproduction and sex determination, loss of conserved pathways in derived fungal lineages that are retained in basal fungi, and shared and divergent virulence strategies of successful human pathogens, including dimorphic and trimorphic transitions in form. The overarching conclusion is that fungal pathogens of animals have arisen repeatedly and independently throughout the fungal tree of life, and while they share general properties, there are also unique features to the virulence strategies of each successful microbial pathogen.

Microbial pathogens in the fungal kingdom. (2011) Fungal Biology Reviews 25(1): 48-60

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As the number of immunocompromised individuals grows, fungal pathogens are becoming ever more important. In this article in Microbiology Today (pdf) Ken Haynes discusses how functional genomics technologies are helping to combat these less than well known eukaryotic adversaries:

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Biologists debated for more than 200 years about which organisms should be counted as fungi. In less than 5 years, DNA sequencing provided a multitude of new characters for analysis and identified about 10 phyla as members of the monophyletic kingdom Fungi. Mycologists benefited from early developments applied directly to fungi. The “universal primers,” so popular in the early 1990s for the polymerase chain reaction (PCR), actually were designed for fungi. Use of the PCR was a monumental advance for those who studied minute, often unculturable, organisms.

Fungi interact with all major groups of organisms. By their descent from an ancestor shared with animals about a billion years ago plus or minus 500 million years, the fungi constitute a major eukaryotic lineage equal in numbers to animals and exceeding plants. But how many fungal species are there?

The Fungi: 1, 2, 3 … 5.1 million species? American Journal of Botany, March 2 2011 doi: 10.3732/ajb.1000298
Premise of the study: Fungi are major decomposers in certain ecosystems and essential associates of many organisms. They provide enzymes and drugs and serve as experimental organisms. In 1991, a landmark paper estimated that there are 1.5 million fungi on the Earth. Because only 70000 fungi had been described at that time, the estimate has been the impetus to search for previously unknown fungi. Fungal habitats include soil, water, and organisms that may harbor large numbers of understudied fungi, estimated to outnumber plants by at least 6 to 1. More recent estimates based on high-throughput sequencing methods suggest that as many as 5.1 million fungal species exist.
Methods: Technological advances make it possible to apply molecular methods to develop a stable classification and to discover and identify fungal taxa.
Key results: Molecular methods have dramatically increased our knowledge of Fungi in less than 20 years, revealing a monophyletic kingdom and increased diversity among early-diverging lineages. Mycologists are making significant advances in species discovery, but many fungi remain to be discovered.
Conclusions: Fungi are essential to the survival of many groups of organisms with which they form associations. They also attract attention as predators of invertebrate animals, pathogens of potatoes and rice and humans and bats, killers of frogs and crayfish, producers of secondary metabolites to lower cholesterol, and subjects of prize-winning research. Molecular tools in use and under development can be used to discover the world’s unknown fungi in less than 1000 years predicted at current new species acquisition rates.

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• There’s an awful lot of zombie ant fungi in Brazil
• The Great Indoors
• New Strain of Virulent Airborne Fungus Looks Set to Spread

Four new fungi in the genus Ophiocordyceps have been identified. These fungi belong to a group of “zombifying” fungi that infect ants and then manipulate their behavior, eventually killing the ants after securing a prime location for spore dispersal.

Beyond this important milestone, the paper also draws attention to undiscovered, complex, biological interactions in threatened habitats. The four new species all come from the Atlantic Rainforest of Brazil which is the most heavily degraded biodiversity hotspot on the planet. Ninety-two percent of its original coverage is gone. The effect of biodiversity loss on community structure is well known. What researchers don’t know is how parasites, such as these zombie-inducing fungi, cope with fragmentation. The authors show that each of the four species is highly specialized on one ant species and has a suite of adaptations and spore types to ensure infection. The life-cycle of these fungi that infect, manipulate and kill ants before growing spore producing stalks from their heads is remarkably complicated. The present work establishes the identification tools to move forward and ask how forest fragmentation affects such disease dynamics.

Hidden Diversity Behind the Zombie-Ant Fungus Ophiocordyceps unilateralis: Four New Species Described from Carpenter Ants in Minas Gerais, Brazil. (2011) PLoS ONE 6(3): e17024. doi:10.1371/journal.pone.0017024
Background: Ophiocordyceps unilateralis (Clavicipitaceae: Hypocreales) is a fungal pathogen specific to ants of the tribe Camponotini (Formicinae: Formicidae) with a pantropical distribution. This so-called zombie or brain-manipulating fungus alters the behaviour of the ant host, causing it to die in an exposed position, typically clinging onto and biting into the adaxial surface of shrub leaves. We (HCE and DPH) are currently undertaking a worldwide survey to assess the taxonomy and ecology of this highly variable species.
Methods: We formally describe and name four new species belonging to the O. unilateralis species complex collected from remnant Atlantic rainforest in the south-eastern region (Zona da Mata) of the State of Minas Gerais, Brazil. Fully illustrated descriptions of both the asexual (anamorph) and sexual (teleomorph) stages are provided for each species. The new names are registered in Index Fungorum (registration.indexfungorum.org) and have received IF numbers. This paper is also a test case for the electronic publication of new names in mycology.
Conclusions: We are only just beginning to understand the taxonomy and ecology of the Ophiocordyceps unilateralis species complex associated with carpenter ants; macroscopically characterised by a single stalk arising from the dorsal neck region of the ant host on which the anamorph occupies the terminal region and the teleomorph occurs as lateral cushions or plates. Each of the four ant species collected – Camponotus rufipes, C. balzani, C. melanoticus and C. novogranadensis – is attacked by a distinct species of Ophiocordyceps readily separated using traditional micromorphology. The new taxa are named according to their ant host.

Pneumocystis species are ascomycetous fungi that obligatorily dwell with no apparent ill effect in the lungs of normal mammals, but they become pathogenic when host defenses are compromised. Identified more than 100 years ago, these atypical fungi manifest characteristics that are unique within the Fungi, such as the lack of ergosterol, genetic complexity of surface antigens, and antigenic variation. Thought to be confined to the severely immunocompromised host, Pneumocystis spp. are being associated with new population niches owing to the advent of immunomodulatory therapies and increased numbers of patients suffering from chronic diseases. The inability to grow Pneumocystis spp. outside the mammalian lung has thwarted progress toward understanding their basic biology, but via the use of new genetic tools and other strategies, researchers are beginning to uncover their biological and genetic characteristics including a biphasic life cycle, significant metabolic capacities, and modulation of lifestyles. This review describes the alternative lifestyles indulged in by these organisms.

Stealth and opportunism: alternative lifestyles of species in the fungal genus Pneumocystis. Annu Rev Microbiol. 2010 64: 431-452

Related:

• Fungal Infections

Candida albicans is the predominant fungal pathogen of humans. In healthy individuals C. albicans is a commensal inhabitant of the gastrointestinal, oral and vaginal tracts. C. albicans can cause superficial infections which, although not life threatening, provide discomfort to the individual and require treatment with antifungals which is a constant drain on hospitals resources. However, C. albicans infections are life threatening when the individual’s immune system becomes compromised as a result of age, cancer, chemotherapy hospitalisation and AIDS. Under these circumstances superficial infections may readily develop into systemic disease where mortality rates are reported to be up to 40%, which is higher than those for most bacterial infections.

Pathogenic microorganisms can produce a variety of secondary metabolites and signalling molecules which can affect the host, or provide them with a selective advantage against competing commensal organisms. This paper demonstrates that gaseous, metabolically generated CO₂ can serve as a signalling molecule to enhance the organism’s virulence during infection establishment by using the fungal pathogen Candida albicans as a model. The researchers identified a CO₂ receptor site within the catalytic domain of the soluble adenylyl cyclase, Cyr1p, which is critical for CO₂ sensing and hence virulence of the organism. CO₂ sensing is conserved in a variety of pathogenic species, and increased levels have been shown to suppress the host’s immune system. CO₂ sensing may represent a mechanism to enhance C. albicans virulence when the host’s immune system is suppressed.

CO₂ Acts as a Signalling Molecule in Populations of the Fungal Pathogen Candida albicans. (2010) PLoS Pathog 6(11): e1001193. doi:10.1371/journal.ppat.1001193
When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO₂ acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO₂-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO₂/bicarbonate regulation of Cyr1p. Disruption of the CO₂/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO₂ sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO₂-signalling system.

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• New Mechanism Fundamental to the Spread of Invasive Yeast
• Statins and Candida

From the outside and within, we are constantly bombarded with a myriad of diverse microbial species. However, our bodies are equipped with an evolutionarily conserved innate immune defense system that allows us to thwart potential pathogens. Antimicrobial peptides (AMPs) are a unique and assorted group of molecules produced by living organisms of all types, considered to be part of the host innate immunity. These peptides demonstrate potent antimicrobial activity and are rapidly mobilized to neutralize a broad range of microbes, including viruses, bacteria, protozoa, and fungi. More significantly, the ability of these natural molecules to kill multidrug-resistant microorganisms has gained them considerable attention and clinical interest. With the growing microbial resistance to conventional antimicrobial agents, the need for unconventional therapeutic options has become urgent. This article provides an overview of AMPs, their biological functions, mechanism of action, and applicability as alternative therapeutic agents.

Presently, AMPs represent one of the most promising future strategies for combating infections and microbial drug resistance. This is evident by the increasing number of studies to which these peptides are subjected. As our need for new antimicrobials becomes more pressing, the question remains: can we develop novel drugs based on the design principles of primitive molecules?

Antimicrobial Peptides: Primeval Molecules or Future Drugs? (2010) PLoS Pathog 6(10): e1001067. doi:10.1371/journal.ppat.1001067

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• Antimicrobial Peptides
• Frogs vs Bacteria

Eben Bayer talks about MycoBond, a technology that uses a filamentous fungi to transform agricultural waste products into strong composite materials. MycoBond products include packaging and styrofoam substitute and in-development rigid insulation board for builders. These products require less energy to create than synthetics like foam, because they’re quite literally grown. Equally compelling, at the end of their useful life, they can be composted or used as garden mulch.

Fungi reproduce both sexually and asexually, producing a vast array of structures which have evolved over time to suit habitat and in some cases host. These structures are of great economic importance to society. Approximately 48% of the world’s food crop yield is lost due to plant diseases, of which the majority are caused by fungi. For most fungal diseases, the primary sources of inoculum are sexual and/or asexual spores. As well as economic losses, fungi can have positive economic benefits for agriculture, such as biocontrol of plant diseases. Numerous fungi have been successfully developed as biocontrol agents (BCAs) of plant diseases and the majority of these are sold as spore preparations.

The global fungal BCA market is dominated by species of the ubiquitous ascomycete Trichoderma. In general, commercial preparations of Trichoderma spp. for biological control consist of bulk-produced conidia (asexual spores), but good biocontrol activity in the environment relies upon the fungus remaining vegetative, and thus antagonistically active. The ideal Trichoderma BCA produces ample conidia in a cost-effective manner during production and maintains long periods of vigorous vegetative growth during usage. Understanding the factors that control this morphogenic switch from mycelia to conidia is integral to biocontrol research. Over 50 years of studies on conidiation in the genus have established Trichoderma as a model for asexual reproduction in fungi. This review presents what is known about the physiological responses of Trichoderma to the environmental cues that induce conidiation, and provides insights into the molecular basis of these responses, including an examination of the signal transduction pathways which link environmental signals to physiological outputs. Understanding species-specific differences in metabolic adaptations to the environment should assist biocontrol design and implementation. Knowledge of the appropriate conditions for maximal yields of viable spores would likely reduce production costs. Knowledge of survivability and vigour within a complex environment could enable targeting of biocontrol strains to the soil or foliar condition appropriate for their species. It may also be possible to create designer BCAs which incorporate desired traits through protoplast fusion or genetic modification.

Reproduction without sex: conidiation in the filamentous fungus Trichoderma. Microbiology 2010 156: 2887-2900
Trichoderma spp. have served as models for asexual reproduction in filamentous fungi for over 50 years. Physical stimuli, such as light exposure and mechanical injury to the mycelium, trigger conidiation; however, conidiogenesis itself is a holistic response determined by the cell’s metabolic state, as influenced by the environment and endogenous biological rhythms. Key environmental parameters are the carbon and nitrogen status and the C:N ratio, the ambient pH and the level of calcium ions. Recent advances in our understanding of the molecular biology of this fungus have revealed a conserved mechanism of environmental perception through the White Collar orthologues BLR-1 and BLR-2. Also implicated in the molecular regulation are the PacC pathways and the conidial regulator VELVET. Signal transduction cascades which link environmental signals to physiological outputs have also been revealed.

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• Bacterial endophytes
• High Tech Fungi