MicrobiologyBytes

Sporulation is a strategy used by many organisms, including bacteria, fungi, protozoa, algae, and ferns to survive conditions that are too harsh to sustain vegetative growth. Survival is generally facilitated by developing specialized cells (spores) with physical properties that confer resistance to environmental assault. Many organisms also produce spores on specialized structures that are adapted for efficient dispersal via wind or water currents. Through these adaptations, sporulation is an effective mechanism to either persist until local conditions improve or disperse to new environments conducive for growth.

For pathogenic microbes, favorable growth conditions are often found in a mammalian host, resulting in serious consequences for human health. For example, spores of protozoan parasites, such as the oocytes of Cryptosporidium sp., can be found in untreated or fecal waste-contaminated water and have been estimated to cause >50% of water-borne parasitic disease worldwide, including major outbreaks in the United States. Spores of bacterial pathogens, such as those produced by Bacillus anthracis, are extremely resistant to physical and chemical insult, making B. anthracis a potentially devastating biological weapon. In fungi, spores are thought to be the infectious particles of many fungal pathogens. This has been shown rigorously for a number of plant fungal pathogens, such as the wheat rusts, Puccinia sp., which disperse globally on an annual basis and cause damage to food crops totaling 3 billion dollars per year.

Among human fungal pathogens, spores are presumed infectious particles for many organisms. The infection-causing potential of spores from human fungal pathogens is exemplified by Coccidioides immitis, as few as 10 spores can establish disease and cause fatal disease. Because these highly infectious spores are adapted for wind dispersal, C. immitis spores, similar to spores from B. anthracis, have been postulated to be serious threats as biological weapons. Despite the demonstrated capacity of spores from human fungal pathogens to infect mammalian hosts, the specific roles that spores play in establishing disease are less clear.

Dueling in the lung: how Cryptococcus spores race the host for survival. Curr Opin Microbiol. Jun 4 2010
Many human fungal pathogens infect people when they are inhaled as spores. Despite the serious impact of fungal spores on human health, little is known about their basic properties or how they interact with the host. This is particularly true for Cryptococcus neoformans, a human fungal pathogen that causes more than 600,000 deaths annually. Spores of C. neoformans have not been well characterized previously because of technical challenges in isolating them; however, recent advances in spore isolation have lead to the first direct analyses of spores. Novel insights into the spore-host interaction, specifically how spores interact with alveolar macrophages, have provided a new model of cryptococcosis that could have broad implications for human fungal pathogenesis.

Related:

• New Strain of Virulent Airborne Fungus Looks Set to Spread
• Anthrax and other spore-forming bacteria (video)

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

In mammals, adenosine assumes an essential role in regulating innate and acquired immune responses. Strong or excessive host inflammatory responses, e.g. in response to bacterial infection, exacerbate the tissue damage inflicted by invading pathogens. Successful immune clearance of microbes therefore involves the balancing of pro- and anti-inflammatory mediators. The cytokines IL-4, IL-10, IL-13, and TGF-β play a role in restricting excessive inflammation, but only adenosine is able to completely suppress immune responses. The immunoregulatory attributes of adenosine are mediated via four transmembrane adenosine receptors: A1, A2A, A2B, and A3. T lymphocytes express the high affinity A2A receptor as well as the low affinity A2B receptor. Depending on their activation state, macrophages and neutrophils express all four adenosine receptors, whereas B cells harbor only A2A. Engagement of A2A inhibits IL-12 production, increases IL-10 in monocytes and dendritic cells, and decreases cytotoxic attributes and chemokine production in neutrophils. Generation of adenosine at sites of inflammation, hypoxia, organ injury, and traumatic shock is mediated by two sequential enzymes.

Although extracellular adenosine is essential for the suppression of inflammation, build-up of excess adenosine is also detrimental. This is exemplified in patients with a deficiency in adenosine deaminase, an enzyme that converts adenosine to inosine. Adenosine deaminase deficiency causes severe compromised immunodeficiency syndrome, with impaired cellular immunity and severely decreased production of immunoglobulins. As the regulation of extracellular adenosine is critical in maintaining immune homeostasis, perturbation of adenosine levels is likely to affect host immune responses during infection.

Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. Scientists examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A (AdsA), a cell wall–anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. Staphylococcal synthesis of adenosine in blood, escape from phagocytic clearance, and subsequent formation of organ abscesses were all dependent on adsA and could be rescued by an exogenous supply of adenosine. An AdsA homologue was identified in the anthrax pathogen Bacillus anthracis, and adenosine synthesis also enabled escape of B. anthracis from phagocytic clearance. Collectively, these results suggest that staphylococci and other bacterial pathogens exploit the immunomodulatory attributes of adenosine to escape host immune responses.

Staphylococcus aureus synthesizes adenosine to escape host immune responses. J. Exp. Med. 28 Sep 2009 doi:10.1084/jem.20090097

Related:
Staphylococcus aureus: superbug
Evolution and pathogenesis of Staphylococcus aureus

Nice introduction on YouTube:

Related:

• Novel method predicts impact of anthrax release

The force of Bacillus anthracis, the ancient scourge that causes anthrax, can sweep through and overpower a two-ton animal in under 72 hours. But when it isn’t busy claiming livestock and humans throughout the world – up to 100,000 annually – it resides ominously in the soil as a spore waiting for its next victim. Researchers now reveal that this deadly bacterium isn’t the only master of its fate. Its survival is directed and shaped by the DNA of bacteria-infecting viruses in what appears to be an evolutionary contract written to benefit both parties. The research revamps the way scientists think about how pathogens exist in the environment in between outbreaks, focusing on the role viruses play during this dormant stage in the life cycle. The implications reach far and wide, from the sequencing of genomes to the recurrent and cyclical nature of disease.

B. anthracis leads a much more complicated life than we had ever known. Small, infecting viruses dramatically alter the survival capabilities of B. anthracis. It is more or less a symbiotic relationship in which the interests of both the bacterium and virus are kept in balance. The secret life of anthrax-causing bacteria emerged from a seemingly innocuous observation made by Louis Pasteur more than 100 years ago. The famous bacteriologist found that earthworms were associated with anthrax-infected animal carcasses in the ground and hypothesized that the earthworm could play an important role in the life cycle of the deadly pest. For the first time, scientists have now confirmed Pasteur’s early hunch. They found that in the gut of the earthworm, B. anthracis infected with bacteriophages live longer than virus-free bacteria. The gut of the earthworm provides the infected bacteria with a safe niche in which to exist.

The researchers further show that in both the gut of the earthworm and the stark confines of a Petri dish, viruses can alter the lifestyle of B. anthracis in two principal ways. One is associated with the ability to build communities, the state in which bacteria prefer to live in the environment; the other affects the bacterium’s ability to produce spores: round, dormant cells with a thick cell wall that enables them to endure harsh environmental conditions that the rod-shaped bacteria cannot. What is more, they found that depending on the conditions of the environment, the virus’s DNA manipulates the bacterium’s genome to toggle between spore production and community building. The relationship appears to result from some sort of evolutionary contract that keeps the interests of bacterium and virus in balance. Since viruses cannot infect and grow in spores, they have an interest in silencing genes that ramp up spore production and in activating genes that help build B. anthracis communities. But when soil conditions threaten the survival of anthrax-causing bacteria, spawning a tougher line of defense to weather the soil’s extreme conditions benefits both parties.

The unveiling of the bacterium’s life cycle opens up completely new strategies to combat anthrax infection. In it was shown that infected anthrax-causing bacteria become more resistant to a natural antibiotic found in the soil. The new studies now go further, showing how these survival capabilities are not just affected by bacteriophages but actually depend on them. Bacteriophages exert their control via molecules known as sigma factors, which delegate proteins to turn specific host genes on or off. Different viruses encode different sigma factors, so the appearance of different traits depends on which virus infects the bacterium. While the DNA of some bacteriophages gets incorporated into the bacterium’s single chromosome, the DNA of others exists as separate circular entities called episomes. These episomes can either stay inside one bacterium or flit in and out, infecting several bacteria in a matter of hours. The finding has implications for the sequencing of genomes. There are more than 1,000 known isolates of anthrax and there is little genetic variation between one isolate and the next. But the phage DNA, which works together with the anthrax genome, has been overlooked. If bacteriophages can govern the fate of bacteria and bacteria affect human health, the transformation of these bacteria may be able to explain the recurrent and cyclical nature of certain diseases. Humans have 10 times more bacteria on them or in them than the number of human cells. And there are 10 times more bacteriophages than there are bacteria.

The Secret Life of the Anthrax Agent Bacillus anthracis: Bacteriophage-Mediated Ecological Adaptations. 2009 PLoS ONE 4(8): e6532. doi:10.1371/journal.pone.0006532
Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities.

Related:

• A bacteriophage contributes to the pathogenicity of the plague bacillus
• Bacteriophage lysogeny
• Novel method predicts impact of anthrax release
• Incidence of bacteriophage lysogeny in temperate and extreme soil environments

Releasing highly pathogenic organisms into an urban population is a act of bioterrorism that could result in a large number of casualties. The first indication that a covert open-air release has occurred is quite likely to be individuals reporting for medical attention. If such an attack is suspected, then public health authorities would attempt to identify those individuals who have been infected in order to provide rapid treatment with the aim of reducing the possibility of disease and potential death. Aiming treatment at too small an area might miss individuals infected further down and/or up wind, whereas issues surrounding both treatment resources and serious side effects may rule out mass treatment campaigns of large sections of the population.

A new paper describes a statistical method that can estimate the origin and time of an aerosolized release of anthrax following detection of the first few cases. The method predicts where the most critically affected areas will be following the release of this highly pathogenic agent, which may enable preventative treatment of individuals at risk and protection from the disease. Previously published methods can estimate the date and scale of anthrax release but not the source location or geographic extent of human exposure. The new method uses information about the first people infected, including when they started to experience symptoms of infection and where they live and work, combined with recent weather information, such as wind direction. Anthrax has the potential to cause a large number of deaths in the event of a covert, open air release. If such a release were to occur, it is critical for public health decision makers to evaluate its extent and the potential impact on the population and then to identify the people most at risk of infection as soon as possible. It is critical to treat people as soon as possible after exposure to anthrax. While forecasts based on small numbers of early cases are less reliable than those obtained later in an outbreak, treating individuals based on early estimates is still likely to save lives overall.

Estimating the Location and Spatial Extent of a Covert Anthrax Release. 2009 PLoS Comput Biol 5(1): e1000356
Rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. Previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. We extend the scope of these methods by proposing a method for characterizing the time, strength, and also the location of an aerosolized pathogen release. A back-calculation method is developed allowing the characterization of the release based on the data on the first few observed cases of the subsequent outbreak, meteorological data, population densities, and data on population travel patterns. We evaluate this method on small simulated anthrax outbreaks (about 25–35 cases) and show that it could date and localize a release after a few cases have been observed, although misspecifications of the spore dispersion model, or the within-host dynamics model, on which the method relies can bias the estimates. Our method could also provide an estimate of the outbreak’s geographical extent and, as a consequence, could help to identify populations at risk and, therefore, requiring prophylactic treatment. Our analysis demonstrates that while estimates based on the first ten or 15 observed cases were more accurate and less sensitive to model misspecifications than those based on five cases, overall mortality is minimized by targeting prophylactic treatment early on the basis of estimates made using data on the first five cases. The method we propose could provide early estimates of the time, strength, and location of an aerosolized anthrax release and the geographical extent of the subsequent outbreak. In addition, estimates of release features could be used to parameterize more detailed models allowing the simulation of control strategies and intervention logistics.

PLoS Pathogens is two years old, and to celebrate, they’ve just published a list of the top ten papers downloaded from September 2005 to July 2007, so if you need to catch up on your reading:

1. Carrageenan Is a Potent Inhibitor of Papillomavirus Infection
   Sexually transmitted human papillomavirus (HPV) infections are very common. Although most HPV infections don’t cause noticeable symptoms, persistent infection with some genital HPV types can lead to cervical cancer or other anal/genital cancers. Another subset of HPV types can cause genital warts. Recent studies have suggested that condoms are not highly effective in preventing HPV infection. Although HPV vaccines will soon become available, they probably will not protect against all genital HPV types and will be too expensive for use in the developing world. Inexpensive HPV-inhibitory compounds (known as topical microbicides) might be useful for blocking the spread of HPV. Using a newly developed cell culture–based HPV inhibition test, we have discovered that an inexpensive gelling agent called carrageenan is an unexpectedly potent HPV infection inhibitor. Carrageenan is also under investigation as a topical microbicide targeting HIV and herpes viruses, but it is a thousand times more effective against HPV in cell culture tests. Interestingly, carrageenan is used as a thickener in some commercially available sexual lubricants and lubricated condoms. Several of these commercial lubricant products are potent HPV inhibitors in our cell culture–infection system. Clinical trials are needed to determine the effectiveness of carrageenan as a topical microbicide against HPV.
2. Modulation of Tumor Necrosis Factor by Microbial Pathogens
   In response to invasion by microbial pathogens, host defense mechanisms get activated by both the innate and adaptive arms of the immune responses. TNF (tumor necrosis factor) is a potent proinflammatory cytokine expressed by activated macrophages and lymphocytes that induces diverse cellular responses that can vary from apoptosis to the expression of genes involved in both early inflammatory and acquired immune responses. A wide spectrum of microbes has acquired elegant mechanisms to overcome or deflect the host responses mediated by TNF. For example, modulatory proteins encoded by multiple families of viruses can block TNF and TNF-mediated responses at multiple levels, such as the inhibition of the TNF ligand or its receptors, or by modulating key transduction molecules of the TNF signaling pathway. Bacteria, on the other hand, tend to modify TNF-mediated responses specifically by regulating components of the TNF signaling pathway. Investigation of these diverse strategies employed by viral and bacterial pathogens has significantly advanced our understanding of both host TNF responses and microbial pathogenesis. This review summarizes the diverse microbial strategies to regulate TNF and how such insights into TNF modulation could benefit the treatment of inflammatory or autoimmune diseases.
3. Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant
   Prostate cancer is the most frequent cancer and the second leading cause of cancer deaths in US men over the age of 50. Several genetic factors have been proposed as potential risk factors for the development of prostate cancer, including a viral defense gene called RNASEL. A common genetic variant in this gene, R462Q, was recently implicated in up to 13% of prostate cancer cases. Given the antiviral role of RNASEL, the authors sought to examine if a virus might be present in prostate cancers associated with the R462Q variant. Using a DNA microarray designed to detect all known viral families, the authors identified a novel virus, named XMRV, in a subset of prostate tumor samples. Polymerase chain reaction testing of 86 prostate tumors for the presence of XMRV revealed a strong association between the presence of the virus and being homozygous for the R462Q variant. Cloning and sequencing of the virus showed that XMRV is a close relative of several known xenotropic murine leukemia viruses. This report presents the first documented cases of human infection with a xenotropic retrovirus. Future work will address the potential connection between XMRV infection and the increased prostate cancer risk in patients with the R462Q RNASEL variant.
4. Human Neutrophils Kill Bacillus anthracis
   Bacillus anthracis is the bacterium that causes anthrax, a disease that can occur through natural infections and also through intentional release. B. anthracis makes spores, which are in a dormant state, similar to seeds of a plant, and are extremely resistant to the environment. B. anthracis spores can infect through the skin or the lung. Lung infections disseminate through the body and are lethal. In contrast, skin infections often remain localized, and patients survive even without treatment. It is not well understood why these bacteria cause a localized infection through the skin and a lethal disease through the lung. Little is known about how B. anthracis is controlled. Neutrophils are the first white blood cells recruited to a site of infection and are specialized in killing microbes. Previous studies show that neutrophils are abundant in the skin form, but not in the lung form of anthrax. The researchers report that human neutrophils can take up B. anthracis spores. Once inside, the spores germinate to form vegetative bacteria. The vegetative bacteria are extremely susceptible to neutrophil-killing mechanisms. The B. anthracis virulence factors (molecules that make bacteria cause diseases) manipulate other human cells but do not deter neutrophils. B. anthracis is indeed exquisitely sensitive to the neutrophil protein α-defensin. These data support a new model where B. anthracis skin, but not lung, infections are controlled by the antimicrobial activity of neutrophils.
5. A Novel Bacterium Associated with Lymphadenitis in a Patient with Chronic Granulomatous Disease
   As new bacteria continue to be discovered every year, it is inevitable that some of them will be found to cause human disease. The authors describe the isolation and characterization of a new bacterium, grown from a patient with chronic granulomatous disease (CGD). In this genetic disease, one of the main lines of defense against infection, the neutrophil, has a discrete defect in the generation of superoxide, leading to recurrent infections with a narrow spectrum of bacteria and fungi. This new organism was cultured from lymph nodes that had been inflamed for several months. To prove that this new bacterium was indeed a pathogen, Greenberg and colleagues measured specific antibody response in the patient: they inoculated CGD mice with this organism and reproduced the appearance of the human infection; they recovered the organism in pure growth from infected mouse spleens. This new bacterium belongs to the family Acetobacteraceae, bacteria that are found widely in the environment. They have a variety of industrial uses, such as the production of vinegar, but have never been reported to cause invasive human disease. Disease-causing organisms remain to be discovered. The researchers outline some of the steps that can be taken to verify the pathogenicity of novel organisms.
6. Gene-Specific Countermeasures against Ebola Virus Based on Antisense Phosphorodiamidate Morpholino Oligomers
   Ebola virus (EBOV) causes a highly lethal hemorrhagic fever that results in up to 50%–90% mortality in humans. There are currently no available vaccines or therapeutics to treat EBOV infection. To date, multiple pre- and post-exposure therapeutic strategies, primarily focused on bolstering the host immune response or inhibiting viral replication, have been undertaken with limited success. Here, Bavari and colleagues report the development of a successful therapeutic regimen for EBOV infection based on antisense phosphorodiamidate morpholino oligomers (PMOs). PMOs are a subclass of chemically modified antisense oligonucleotides that interfere with the translation of viral mRNA, thus inhibiting viral amplification. Using a cell-free translation system, a cell-based assay, and survival studies in rodents, we identified several efficacious EBOV-specific PMOs. Further, prophylactic administration of a combination of three EBOV-specific PMOs specifically targeting VP24, VP35, and the viral polymerase L protected rhesus macaques from lethal EBOV infection. This is the first successful antiviral intervention against filoviruses in nonhuman primates. These findings may serve as the basis for a new strategy to quickly develop virus-specific therapies in defense against known, emerging, and genetically engineered bioterrorism threats.
7. The Role of Innate Immune Responses in the Outcome of Interspecies Competition for Colonization of Mucosal Surfaces
   Bacterial infection commonly begins with organisms that colonize and proliferate on mucosal surfaces. These microenvironments may be occupied by multiple microbial species, suggesting that successful colonizers are distinguished by their capacity to prevail over their competitors. This study examines interactions between two bacterial species that both colonize and infect the human upper respiratory tract. In a mouse model, strains of both Haemophilus influenzae and Streptococcus pneumoniae efficiently colonize the nasal mucosa when tested individually. In contrast, following co-inoculation, H. influenzae rapidly and completely outcompetes S. pneumoniae. This competitive effect is dependent on the local responses from the host in the form of a specific type of white blood cell (neutrophil) that acts to engulf and kill microorganisms that have been labeled by proteins that bind to microbial surfaces (complement). The results of this study show that recognition of microbial products from one species may activate inflammatory responses that promote the clearance of another competing species. This study also demonstrates how manipulations such as antibiotics or vaccines, which are meant to diminish the presence of a single pathogen, may inadvertently alter the competitive interactions of complex microbial communities.
8. Prions Adhere to Soil Minerals and Remain Infectious
   Transmissible spongiform encephalopathies (TSEs) are a group of incurable diseases likely caused by a misfolded form of the prion protein (PrP^Sc). TSEs include scrapie in sheep, bovine spongiform encephalopathy (“mad cow” disease) in cattle, chronic wasting disease (CWD) in deer and elk, and Creutzfeldt-Jakob disease in humans. Scrapie and CWD are unique among TSEs because they can be transmitted between animals, and the disease agents appear to persist in environments previously inhabited by infected animals. Soil has been hypothesized to act as a reservoir of infectivity, because PrP^Sc likely enters soil environments through urinary or alimentary shedding and decomposition of infected animals. In this manuscript, the authors test the potential for soil to serve as a reservoir for PrP^Sc and TSE infectivity. They demonstrate that PrP^Sc binds to a variety of soil minerals and to whole soils. They also quantitate the levels of protein binding to three common soil minerals and show that the interaction of PrP^Sc with montmorillonite, a common clay mineral, is remarkably strong. PrP^Sc bound to Mte remained infectious to laboratory animals, suggesting that soil can serve as a reservoir of TSE infectivity.
9. The Expanding Universe of Prion Diseases
   Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP^C. Several mammalian species are affected by the diseases, and in the case of “mad cow disease” (BSE) the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases—including human diseases variant Creutzfeldt-Jakob disease (vCJD) and sporadic fatal insomnia (sFI), bovine amyloidotic spongiform encephalopathy (BASE), and Nor98 of sheep—have been identified in the last ten years, and chronic wasting disease (CWD) of North American deer (Odocoileus Specis) and Rocky Mountain elk (Cervus elaphus nelsoni) is undergoing a dramatic spread across North America. While amplification (BSE) and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk) can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of “sporadic” disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.
10. Crossing the Line: Selection and Evolution of Virulence Traits
    The evolution of pathogens presents a paradox. Pathogenic species are often absolutely dependent on their host species for their propagation through evolutionary time, yet the pathogenic lifestyle requires that the host be damaged during this dependence. It is clear that pathogenic strategies are successful in evolutionary terms because a diverse array of pathogens exists in nature. Pathogens also evolve using a broad range of molecular mechanisms to acquire and modulate existing virulence traits in order to achieve this success. Detailing the benefit of enhanced selection derived through virulence and understanding the mechanisms through which virulence evolves are important to understanding the natural world and both have implications for human health.

Nice work. Open access publishing has come of age.