MicrobiologyBytes

Bats, which are ‘keystone species’ in many ecosystems, play notable roles in plant pollination, forest regeneration and control of insect populations. Bats are important to human health as they are reservoirs or carriers for rabies and other viruses, parasites, and pathogenic fungi. Hibernation is believed to be an important adaptation in bats that may contribute to their exceptional longevity. The common little brown bat (Myotis lucifugus) hibernates, along with the endangered Indiana bat (Myotis sodalis), in many hibernacula in the Northeastern United States, including caves and mines in upstate New York. Hibernating bats can suffer significant mortality due to adverse environmental conditions such as freezing or flooding, as well as human activities including visitation and pesticide applications. No mass mortality was reported until recently from bat sites that had been surveyed for almost three decades by the New York State Department of Environmental Conservation. Recently, however little brown bats have been found to be dying in large numbers at many hibernation sites in upstate New York. This problem has spread to other States in the Northeastern USA.

Morphological and Molecular Characterizations of Psychrophilic Fungus Geomyces destructans from New York Bats with White Nose Syndrome (WNS). PLoS ONE 5(5): e10783. doi:10.1371/journal.pone.0010783
Massive die-offs of little brown bats (Myotis lucifugus) have been occurring since 2006 in hibernation sites around Albany, New York, and this problem has spread to other States in the Northeastern United States. White cottony fungal growth is seen on the snouts of affected animals, a prominent sign of White Nose Syndrome (WNS). A previous report described the involvement of the fungus Geomyces destructans in WNS, but an identical fungus was recently isolated in France from a bat that was evidently healthy. The fungus has been recovered sparsely despite plentiful availability of afflicted animals.
We have investigated 100 bat and environmental samples from eight affected sites in 2008. Our findings provide strong evidence for an etiologic role of G. destructans in bat WNS. (i) Direct smears from bat snouts, Periodic Acid Schiff-stained tissue sections from infected tissues, and scanning electron micrographs of bat tissues all showed fungal structures similar to those of G. destructans. (ii) G. destructans DNA was directly amplified from infected bat tissues, (iii) Isolations of G. destructans in cultures from infected bat tissues showed 100% DNA match with the fungus present in positive tissue samples. (iv) RAPD patterns for all G. destructans cultures isolated from two sites were indistinguishable. (v) The fungal isolates showed psychrophilic growth. (vi) We identified in vitro proteolytic activities suggestive of known fungal pathogenic traits in G. destructans.
Further studies are needed to understand whether G. destructans WNS is a symptom or a trigger for bat mass mortality. The availability of well-characterized G. destructans strains should promote an understanding of bat–fungus relationships, and should aid in the screening of biological and chemical control agents.

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• Colony Collapse Disorder

Emerging and reemerging infectious diseases are increasing worldwide and represent a major public health concern. One class of emerging human and animal diseases is caused by fungi. A new study examines an outbreak of a fungal infection, Cryptococcus gattii, in the Pacific Northwest of the United States. This fungus has been considered a tropical fungus, but emerged to cause an outbreak in the temperate climes of Vancouver Island in 1999 that is now causing disease in humans and animals in the United States. Because of the way an Oregon-specific strain of the fungus is reproducing and spreading, it will likely move into California and other adjacent areas. This novel fungus is worrisome because it appears to be a threat to otherwise healthy people. Typically, we more often see this fungal disease associated with transplant recipients and HIV-infected patients, but that is not what we are seeing in this case. VGIIc, the new Oregon strain, has yielded dozens of isolates from many specimens, including domesticated animals like cats, dogs and sheep – even an unlucky alpaca. Most of those are nonmigratory animals, which suggests that the animals probably didn’t bring the pathogen from some other region but, rather, acquired it locally. Using molecular techniques, the geneticists uncovered clues that showed the Oregon-only fungal strain most likely arose recently, parallel to the outbreak of C. gattii that began in Canada in 1999 that has now spread into Washington and Oregon.

The researchers found that the novel genotype (VGIIc) is now a major source of C. gattii illness in Oregon. Because C. gattii types had previously been found in tropical areas, the authors speculate that environmental changes may be responsible for the evolution and emergence of this pathogen. Determining the exact origin of the VGIIc type is difficult, and sampling thus far has failed to turn up isolates in Oregon soil, water or trees. The mortality rate for recent C. gattii cases in the Pacific Northwest is running at approximately 25 percent, or 5 out of 21 cases analyzed in the United States, compared to a mortality rate of 8.7 percent of 218 cases in British Columbia, Canada. Most C. gattii infections follow a more complicated clinical course in people than does the more common Cryptococcus neoformans. Symptoms can appear two to several months after exposure, and while most people never develop symptoms, those infected may have a cough lasting weeks, sharp chest pain, shortness of breath, headache (related to meningitis), fever, night time sweats and weight loss. In animals the symptoms are a runny nose, breathing problems, nervous system problems and raised bumps under the skin. While C. gattii can be treated, it cannot be prevented; there is no vaccine. Because the strain is so virulent when it infects some humans and animals, the researchers are calling for greater awareness and vigilance in testing. Some strains of C. gattii are not more virulent than C. neoformans, for example, but doctors need to know what type they are dealing with.

Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States. PLoS Pathog 6(4): e1000850. doi:10.1371/journal.ppat.1000850
Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions including mainland British Columbia and the United States. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness in the region. Through molecular epidemiology and population analysis of MLST and VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination in the global VGII population. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Our evidence documents emerging hypervirulent genotypes in the United States that may expand further and provides insight into the possible molecular and geographic origins of the outbreak.

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• All About Fungi: Part 1
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Most of my work over the last few years has been involved with science education, and much of the online effort has gone into surfacing aspects of the scientific literature by making it accessible to a student audience, and indeed the general public, should they be interested. Mostly, this has meant developing the MicrobiologyBytes website, along with its Twitter, Friendfeed and Facebook satellites. In my “education hat on” guise, I write frequently online about my work on Science of the Invisible, Twitter and Friendfeed. So why would I need another public outlet?

Open notebook science (ONS) is the practice of making the primary record of a research project publicly available online as it is generated. This involves placing the personal, or laboratory, notebook of the researcher(s) online along with all raw and processed data, and any associated material. The approach can be summed up by the slogan “no insider information”. This is far from the norm of scientific practice, but over the last year of talking to some of the leading practitioners of ONS, notably Jean-Claude Bradley and Cameron Neylon, I have become convinced that I would like to try it. One part of our feasibility test is a new blog, a space where our part-formed thoughts, ideas, planning, and general commentary on ONS stuff will appear. The other part is our open notebook on Wikispaces, where all the data will be posted. If you want to follow our progress, subscribe to the RSS feed for this blog, or go to this page and subscribe with the feed reader of your choice. If you prefer, you can receive updates via your email account.

Open or closed? It’s not that simple. There are many flavours of ONS, and it’s not clear yet which one(s) we want or are able to pursue. Indeed, our style of “open” is one of the first things we need to work out about this project. For a variety of reasons, not all of the research done in our laboratory will switch to ONS. Initially, we intend to try it out with a new project we are developing (which is described below). Thus our approach to ONS is itself an experiment. Only time will tell if we are able or willing to continue in this format. Apart from funding, it depends whether this idea wins hearts and minds – not only in our lab, but beyond it. In part, that depends how much interaction we receive. the project we are beginning is a new field for us, so we don’t expect the world to be queuing up to help us, but to be successful, the downside risk of ONS needs to be balanced by the upside of helpful positive interactions from interested observers.

So what about the science?

The chytrid fungus Batrachochytrium dendrobatidis (Bd) is an emerging pathogen of amphibians worldwide. The aquatic zoospores of this primitive fungus infect larval or adult amphibians, and, depending on the host species and other factors as yet unknown, may cause anything from 0-100% mortality. Coupled with climate change, pollution and habitat loss, chytridiomycosis (or “chytrid”, pronounced “kit-rid”) is a serious threat to many amphibian species. Bd research has moved from obscurity to prominence very rapidly over the past few years, and two complete genome sequences are available (JAM81, JEL423):

http://dan.corlan.net/medline-trend.html

So where do we fit in?

We are trying to leverage our existing skills in molecular biology, antibody production, protein chemistry and microbiology to study this organism. In part, this is because of an interest in the environmental impact of this emerging pathogen, but we are also interested in studying Bd as a model organism to examine aspects of fungal biology and pathogenesis. We are currently interested in developing work in the following areas:

Aedes aegypti is the urban vector of dengue viruses worldwide. While climate influences the geographical distribution of this mosquito species, other factors also determine the suitability of the physical environment for this mosquito. Importantly, the close association of Ae. aegypti with humans and the domestic environment allows this species to persist in regions that may otherwise be unsuitable based on climatic factors alone. This review highlights the need to incorporate the impact of the urban environment in attempts to model the potential distribution of Ae. aegypti and briefly discuss the potential for future technology to aid management and control of this widespread vector species.

The dengue vector Aedes aegypti: What comes next. Microbes Infect. Jan 20 2010. doi:10.1016/j.micinf.2009.12.011

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• Pathogenic Flaviviruses

There is strong evidence to suggest that climate change has, and will continue to affect the occurrence, distribution and prevalence of livestock diseases in Great Britain (GB). This paper reviews how climate change could affect livestock diseases in GB. Factors influenced by climate change and that could affect livestock diseases include the molecular biology of the pathogen itself; vectors (if any); farming practice and land use; zoological and environmental factors; and the establishment of new microenvironments and microclimates. The interaction of these factors is an important consideration in forecasting how livestock diseases may be affected. Risk assessments should focus on looking for combinations of factors that may be directly affected by climate change, or that may be indirectly affected through changes in human activity, such as land use (e.g. deforestation), transport and movement of animals, intensity of livestock farming and habitat change. A risk assessment framework is proposed, based on modules that accommodate these factors. This framework could be used to screen for the emergence of unexpected disease events.

The effect of climate change on the occurrence and prevalence of livestock diseases in Great Britain: a review. J Appl Microbiol. (2009) 106(5): 1409-1423

Related:

• Bluetongue virus
• MicrobiologyBytes: Climate Change

The flavivirus genus includes viruses with a remarkable ability to produce disease on a large scale. The expansion and increased endemicity of dengue and West Nile viruses in the Americas exemplifies their medical and epidemiological importance. The rapid detection of virus infection and induction of the innate antiviral response are crucial to determining the outcome of infection. The intracellular pathogen receptors RIG-I and MDA5 play a central role in detecting flavivirus infections and initiating a robust antiviral response. Yet, these viruses are still capable of producing acute illness in humans. It is now clear that flaviviruses utilize a variety of mechanisms to modulate the interferon response. The non-structural proteins of the various flaviviruses reduce expression of interferon dependent genes by blocking phosphorylation, enhancing degradation or down-regulating expression of major components of the JAK/STAT pathway. Recent studies indicate that interferon modulation is an important factor in the development of severe flaviviral illness. This suggests that an increased understanding of viral-host interactions will facilitate the development of novel therapeutics to treat these viral infections and improved biological models to study flavivirus pathogenesis.

How Flaviviruses Activate and Suppress the Interferon Response. Viruses 2010, 2(2), 676-691; doi:10.3390/v2020676

Related:

• MicrobiologyBytes: Flaviviruses
• MicrobiologyBytes: Interferon

Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogenic microorganisms and the dynamic relationships between microorganisms, their hosts and the environment.

Emerging infections (EIs) can be defined as “infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range”. EIs have shaped the course of human history and have caused incalculable misery and death. In 1981, a new disease – acquired immune deficiency syndrome (AIDS) – was first recognized. As a global killer, AIDS now threatens to surpass the Black Death of the fourteenth century and the 1918–1920 influenza pandemic, each of which killed at least 50 million people. Of the newly emerging and re-emerging/resurging diseases that have followed the appearance of AIDS, some have been minor curiosities, such as the 2003 cases of monkeypox imported into the United States, whereas others, such as severe acute respiratory syndrome (SARS), which emerged in the same year, have had a worldwide impact. The 2001 anthrax bioterrorist attack in the United States falls into a third category: deliberately emerging diseases. EIs can be expected to remain a considerable challenge for the foreseeable future. Emergence results from dynamic interactions between rapidly evolving infectious agents and changes in the environment and in host behaviour that provide such agents with favourable new ecological niches. This review examines the nature and scope of emerging and re-emerging microbial threats and considers methods for their control.

The challenge of emerging and re-emerging infectious diseases. Nature 430, 242-249, 2004 doi:10.1038/nature02759

Related:

• MicrobiologyBytes: Emerging Diseases

Traditional lab tests for disease diagnosis can be too expensive and cumbersome for the regions most in need. George Whitesides’ ingenious answer is a foolproof tool that can be manufactured at virtually zero cost, as shown in this video:

Coldwater and tropical fish are the third most popular pet in the UK after cats and dogs. Over 3 million homeowners have a pond in their garden and many of these are stocked with fish, some of which, like koi carp, are very expensive. As Keith Way describes in this article in Microbiology Today (pdf) a whole host of viruses are in the environment just waiting to infect them with harmful diseases:

With the discovery of non-filterable disease agents, or viruses, in the late 19th century there came a greater realization of the role that viruses may play in infectious diseases of fish. However, the breakthrough for fish virology came with the general developments in virological techniques that blossomed in the 1950s and 60s. In particular, visualization of viruses by electron microscopy, improvements in protein and nucleic acid analysis and, most significantly, the isolation of viruses on continuous (immortal) fish cell lines. At the same time, aquaculture around the world developed in the 1960s and 70s, and farming of fish and fish-keeping rapidly increased. With these developments and, more recently, the global increase in trade in ornamental fish there has been an increase in new diseases and the emergence of serious virus diseases. Viruses that have caused serious but isolated disease outbreaks in cyprinid species and some ictalurid (catfish) species, and may affect coldwater ornamental fish, include aquareoviruses, coronaviruses, poxviruses and iridoviruses. More serious disease epidemics in ornamental species have been caused by rhabdoviruses and herpesviruses.

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