Radionuclides in the environment are one of the major concerns to human health and ecotoxicology. The explosion at the Chernobyl nuclear power plant renewed interest in the role played by fungi in mediating radionuclide movement in ecosystems. As a result of these studies, our knowledge of the importance of fungi, especially in their mycorrhizal habit, in long-term accumulation of radionuclides, transfer up the food chain and regulation of accumulation by their host plants was increased. Micro-fungi have been found to be highly resilient to exposure to ionizing radiation, with fungi having been isolated from within and around the Chernobyl plant. Radioresistance of some fungal species has been linked to the presence of melanin, which has been shown to have emerging properties of acting as an energy transporter for metabolism and has been implicated in enhancing hyphal growth and directed growth of sensitized hyphae towards sources of radiation. Using this recently acquired knowledge, we may be in a better position to suggest the use of fungi in bioremediation of radioactively contaminated sites and cleanup of industrial effluent.
Fungi appear to be very resistant to radionuclides in the environment. Part of this resistance may be the smaller amount of DNA per nucleus than mammalian cells, but evidence from comparative studies between pigment and nonpigmented fungi suggest there may be other factors that confer radioresistance. Melanin pigment may provide some protection against ionizing radiation and be integral to the absorption and retention of radionuclides. Owing to the long-lived and extensive hyphal network and biomass in upper soil horizons of forest ecosystems, fungi are very efficient in absorbing radionuclides, and are an important component of long term accumulation of radionuclides. This may be why radionuclide adsorption/desorption models do not conform to observed patterns, as mycorrhizal fungi mediate soil-to-plant transfer rates. Internal translocation of radionuclides to and hyper-accumulation into harvestable fruit bodies of macro-fungi has potential for environmental remediation but needs further evaluation.
Today’s issue of Science describes how a group of scientists led by Craig Venter have built an entire bacterial genome from scratch, i.e. starting with simple laboratory chemicals and finishing with a 582,970 base pair DNA chromosome. So is this the end of the world? Have mad scientists created a Frankenstein bug which will escape the laboratory and eat the world?
Nope.
For one thing, the molecule which has been synthesized is presently just that - an inert molecule of DNA. Not until it is inserted into a “hollow” bacterial host from which the DNA has been removed can it come “alive” and start to replicate itself and direct the activities of the cell.
But more importantly, this synthetic biology project is based on an existing organism (Mycoplasma genitalium), which has been around for a long time, so it’s not exactly new. Venter’s team has reproduced this reather than creating anything new.
Finally, some bacteria degrade explosives, others prefer boiling methanol - in other words, if it is possible, nature has already thought of it. So the article published today is nothing to lose sleep over. Of course, that doesn’t mean that at some point in the future those nasty terrorists won’t build a synthetic organism which is genuinely dangerous. But they’re not going to do it working in their garage - this is a government or large corporation-scale project which is the biological equivalent of putting a person on the moon. So if you want something to worry about, worry about climate change, your grades, or the stock market.
Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. 2008 Science Published Online January 24, 2008
We have synthesized a 582,970 bp Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted “watermarks” at intergenic sites known to tolerate transposon insertions. Overlapping “cassettes” of 5 to 7 kb, assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate assemblies of approximately 24 kb, 72 kb (”1/8 genome”), and 144 kb (”1/4 genome”), which were all cloned as bacterial artificial chromosomes (BACs) in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination (TAR) cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments.
The Past:
Plague has given rise to at least three major pandemics. The first (the Justinian plague) spread around the Mediterranean Sea in the 6th century AD, the second (the Black Death) started in Europe in the 14th century and recurred intermittently for more than 300 years, and the third started in China during the middle of the 19th century and spread throughout the world. Purportedly, each pandemic was caused by a different biovar of Yersinia pestis, respectively, Antiqua (still found in Africa and Central Asia), Medievalis (currently limited to Central Asia), and Orientalis (almost worldwide in its distribution). The Present:
Given this history, plague is often classified as a problem of the past. However, it remains a current threat in many parts of the world, particularly in Africa, where both the number of cases and the number of countries reporting plague have increased during recent decades. Following the reappearance of plague during the 1990s in several countries, plague has been categorised as a re-emerging disease.
The Future:
Plague cannot be eradicated, since it is widespread in wildlife rodent reservoirs. Hence, there is a critical need to understand how human risks are affected by the dynamics of these wildlife reservoirs. For example, the likelihood of a plague outbreak in North American and Central Asian rodents, and the resulting risk to humans, is known to be affected by climate. Recent analysis of data from Kazakhstan shows that warmer springs and wetter summers increase the prevalence of plague in its main host, the great gerbil. Such environmental conditions also seem to have prevailed during the emergence of the Second and Third Pandemics - conditions that might become more common in the future.
Plague may not match the so-called “big three” diseases (malaria, HIV/AIDS, tuberculosis; see for example) in numbers of current cases, but it far exceeds them in pathogenicity and rapid spread under the right conditions. It is easy to forget plague in the 21st century, seeing it as a historical curiosity. But in our opinion, plague should not be relegated to the sidelines. It remains a poorly understood threat that we cannot afford to ignore.
In August, most people took a holiday and this was the quietest month of the year in terms of visitors, but we still managed to fit in Hendra, chikungunya and Marburg viruses.
Glanders is an infectious disease which occurs mainly in horses, mules, and donkeys, but can also be contracted by other animals such as dogs, cats and goats. It is caused by infection with the bacterium Burkholderia mallei, usually by ingestion of contaminated food or water. Melioidosis [mel-ee-oi-doh-sis] affects humans as well as animals such as goats, sheep, horses and cattle, and is caused by Burkholderia pseudomallei. Burkholderia species are Gram-negative, non-spore-forming bacteria quite commonly found in soil and water, especially in tropical climates.
Symptoms of glanders in animals include the formation of lesions in the lungs and ulceration of mucous membranes in the upper respiratory tract. The acute form of the disease results in coughing, fever and the release of an infectious nasal discharge, followed by septicaemia and death within days. In the chronic form, nasal and skin nodules develop, eventually forming ulcers. Death can occur within months, while survivors act as carriers. Glanders rarely affects humans and I’ll explain the reason for this shortly.
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In contrast to glanders, melioidosis often affects humans. The mode of infection is through a break in the skin, or through the inhalation of aerosolized B. pseudomallei cells. There is an association with increased rainfall, with the number of cases increasing following heavy rains. The mean incubation period for acute melioidosis is 9 days (range 1-21 days), but patients with latent melioidosis may remain symptom free for decades. The longest known period between presumed exposure and clinical symptoms is 62 years. Melioidosis has a wide spectrum of severity. Patients usually have a fever, but other symptoms such as a cough or chest pains can indicate pneumonia, and bone or joint pains may indicate bone infections or septic arthritis, etc. The treatment of melioidosis is divided into two stages, an intravenous high intensity stage followed by an oral maintenance stage to prevent recurrence. Surgical drainage is usually required for abscesses. Without access to appropriate antibiotics, melioidosis has a mortality rate which exceeds 90%. With appropriate treatment, the mortality rate is about 10% for uncomplicated cases but up to 80% for cases with bacteraemia or severe sepsis.
The unusual genome of Burkholderia pseudomallei has two large chromosomes (most bacteria have only one) and the two chromosomes have different roles (Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei PNAS USA 2004 101: 14240-5). The larger 4.07 megabase pair chromosome contains “standard issue” genes for most of the housekeeping work of the cell, whereas the smaller 3.17 megabase pair chromosome contains genes which allow B. pseudomallei to adapt and survive in a range of environments. A further striking feature of the genome is the presence of 16 genomic islands which together made up 6% of the genome. These are present in clinical and in soil isolates but entirely absent from B. mallei and so may be related to the greater pathologic potential of B. pseudomallei over its close relative.
The infectious dose of B. pseudomallei for humans is not known, but probably varies. Most infections with B. pseudomallei in previously healthy individuals have followed major contamination (e.g. near-drowning episodes, contaminated war wounds, inoculation with contaminated medications or laboratory accidents). However, other cases are thought to have occurred following relatively minor exposure (e.g. inhalation of aerosols by helicopter crews in Vietnam). In some susceptible animals, the lethal dose by inoculation is less than 10 organisms. However, there are only few unusual cases documented for direct person-to-person transmission. In endemic areas, at-risk people (e.g. rice-paddy farmers) are warned to avoid contact with soil, mud and surface water where possible.
Due to the high mortality rate in humans and the small number of organisms required to establish infection, Burkholderia species have been investigated as a potential biological warfare or bioterrorism agents. During World War I, glanders was believed to have been spread deliberately by German agents to infect Russian horses and mules on the Eastern Front. This had an effect on troop and supply convoys as well as on artillery movements, which were then dependent on horses and mules. Both the USA and the Soviet Union are believed to have studied these agents as possible biological warfare weapons during and after World War II, but so far as is known they were never weaponized (i.e. manipulated to form more deadly strains). The features of these bacteria which make them candidates for deliberate release include:
Ability to cause severe, rapidly fatal invasive infections
Ability to initiate infections via aerosols, inoculation and possibly ingestion
Intrinsic resistance to many antibiotics
Ability to infect a wide range of animals as well as humans
Long term persistence in the environment under suitable conditions (there were many human cases of glanders in Russia in the years after World War II)
So far, so bad. But it gets worse. Currently, there is no vaccine available for either B. mallei or B. pseudomallei in humans or animals. Because the presence of antibodies does not appear to be protective, a vaccine must also stimulate the cellular immune response. Burkholderia are intracellular pathogens, and the presence of antibodies does not appear to be protective against disease, so any vaccine must also stimulate cellular immune responses. As a biological weapon, B. pseudomallei lacks some of the immediate terror of anthrax or smallpox, but infections can be very difficult to diagnose (it has been called “the Great Mimicker”), and may occur many decades after exposure to the bacterium. No-one knows how the bacteria survive in the body for so long, but in many late-onset cases, a chronic illness such as diabetes or kidney disease is the spark which ignites the latent infection. And unlike growing smallpox virus, it would be relatively easy for a terrorist group with limited microbiological knowledge to brew up cultures of Burkholderia pseudomallei….
Human disease attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for more than 2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because it has a large, slowly evolving DNA genome, researchers were able to construct a phylogeny of VARV by analyzing single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. The results reveal two primary VARV clades, which are likely to have diverged from an ancestral African rodent-borne variola-like virus either 16,000 or 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. The other primary clade included both alastrim minor, a phenotypically mild smallpox described from the Americas, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP.
Observations of smallpox-typical skin rashes on Egyptian mummies dating from 1100 to 1580 B.C. gave credibility to theories that ancient Egypt was an early (and perhaps the earliest) smallpox endemic region. However, smallpox researchers noted that “The most striking thing about smallpox is its absence from the books of the Old and New Testaments, and also from the literature of the Greeks and Romans. Such a serious disease as variola major is very unlikely to have escaped a description by Hippocrates if it existed.” Historical records from Asia describe evidence of smallpox-like disease in medical writings from ancient China (1122 B.C.) and India (as early as 1500 B.C.). The earliest unmistakable description of smallpox first appears in the 4th century A.D. in China, the 7th century A.D. in India and the Mediterranean, and the 10th century A.D. in southwestern Asia. These early Asian descriptions could indicate that pandemic smallpox originated in East Asia. Sequence analysis indicates that divergence between VARV and rodent poxviruses occurred from 16,000 YBP to 68,000 YBP, and that VARV seems to have evolved from a pathogen of African rodents and subsequently spread out of Africa. On the origin of smallpox: Correlating variola phylogenics with historical smallpox records
PNAS USA 2007 104:15787-15792
What does this all mean?
In spite of concerns about bioterrorism, smallpox is no longer a major human pathogen, but understanding the origin of this disease, which has been of major importance for most of human history, offers glimpses into how we might rapidly understand new emerging diseases as they appear.
For a long time it has been generally believed the the most probable origin for smallpox virus was in Asia, but as with yellow fever and HIV, this new research seems to show that smallpox originally came out of Africa.
EpiSPIDER is a new AJAX web service from the US Centers for Disease Control and Prevention, and provides a web 2.0 style front end for ProMED, the global electronic reporting system monitoring of emerging diseases.
EpiSPIDER provides Google Maps, Graphs, Treemaps, “Sparklines” (timelines) and RSS feeds of email traffic on ProMED mail, and drags ProMED into the web 2.0 era.
Yersinia pestis, the plague bacillus, has an exceptional pathogenicity but the factors responsible for its extreme virulence are still unknown. A genome comparison with its less virulent ancestor Yersinia pseudotuberculosis identified a few Y. pestis-specific regions acquired after their divergence. One of them potentially encodes a prophage (YpfPhi), similar to filamentous phages associated with virulence in other pathogens. YpfPhi forms filamentous phage particles infectious for other Y. pestis isolates. Deletion of the YpfPhi genome does not affect Y. pestis ability to colonize and block the flea proventriculus, but results in an alteration of Y. pestis pathogenicity in mice. Transformation of Y. pestis from a classical enteropathogen to the highly virulent plague bacillus was accompanied by the acquisition of an unstable filamentous phage. Continued maintenance of YpfPhi despite its high in vitro instability suggests that it confers selective advantages to Y. pestis under natural conditions. This study represents the first characterization of a chromosomal element acquired by Y. pestis after its emergence from its recent ancestor Y. pseudotuberculosis and which may have participated in its evolution towards a deadly pandemic pathogen.
Clostridium botulinum is a heterogeneous Gram-positive species that comprises four genetically and physiologically distinct groups of bacteria that share the ability to produce botulinum neurotoxin, the most poisonous toxin known to man, and the causative agent of botulism, a severe disease of humans and animals. We report here the complete genome sequence of a representative of Group I (proteolytic) C. botulinum. The genome consists of a chromosome (3,886,916 bp) and a plasmid (16,344 bp), which carry 3650 and 19 predicted genes, respectively. Consistent with the proteolytic phenotype of this strain, the genome harbors a large number of genes encoding secreted proteases and enzymes involved in uptake and metabolism of amino acids. The genome also reveals a hitherto unknown ability of C. botulinum to degrade chitin. There is a significant lack of recently acquired DNA, indicating a stable genomic content, in strong contrast to the fluid genome of Clostridium difficile, which can form longer-term relationships with its host. Overall, the genome indicates that C. botulinum is adapted to a saprophytic lifestyle both in soil and aquatic environments. This pathogen relies on its toxin to rapidly kill a wide range of prey species, and to gain access to nutrient sources, it releases a large number of extracellular enzymes to soften and destroy rotting or decayed tissues.
Radionuclides in the environment are one of the major concerns to human health and ecotoxicology. The explosion at the Chernobyl nuclear power plant renewed interest in the role played by fungi in mediating radionuclide movement in ecosystems. As a result of these studies, our knowledge of the importance of fungi, especially in their mycorrhizal habit, in long-term accumulation of radionuclides, transfer up the food chain and regulation of accumulation by their host plants was increased. Micro-fungi have been found to be highly resilient to exposure to ionizing radiation, with fungi having been isolated from within and around the Chernobyl plant. Radioresistance of some fungal species has been linked to the presence of melanin, which has been shown to have emerging properties of acting as an energy transporter for metabolism and has been implicated in enhancing hyphal growth and directed growth of sensitized hyphae towards sources of radiation. Using this recently acquired knowledge, we may be in a better position to suggest the use of fungi in bioremediation of radioactively contaminated sites and cleanup of industrial effluent.
We started January off with 
Clostridium botulinum is a heterogeneous 