Saturday Cimema: How mushrooms can save the world

Biofuels from algae

Oil production from algae claimed to be 3-10 times more efficient than producing biofuels from corn:

The number of virus particles transmitted by an insect vector

Plant viruses are submitted to narrow population bottlenecks both during infection of their hosts and during horizontal transmission between host individuals. The size of bottlenecks exerted on virus populations during plant invasion has been estimated in a few systems but is not addressed yet for horizontal transmission. Using competition for aphid transmission between two Potato virus Y variants, one of them being noninfectious but equally transmissible, the authors estimated of the size of bottlenecks exerted on an insect-borne virus during its horizontal transmission. They found that an aphid transmitted on average 0.5-3.2 virus particles, which is extremely low compared with the overall viral population in a plant. Such narrow bottlenecks emphasize the strength of stochastic events acting on virus populations, and illustrate, by modeling virus emergence, why estimating this parameter is important.

Estimation of the number of virus particles transmitted by an insect vector. 2007 PNAS USA 104: 17891-17896

New Drugs for Nasty Nematodes

The nematodes, or roundworms, comprise a large number of pathogens of man and domestic animals. Gastrointestinal nematodes, such as the blood-sucking Haemonchus contortus, are major parasites of ruminants that cause substantial economic losses to livestock production worldwide. In the absence of vaccines for gastrointestinal nematodes, control of infections relies mainly on chemotherapy. Drug resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics - the benzimidazoles, imidazothiazoles and macrocyclic lactones - has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. This paper report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describes the development of drug candidates that are effective against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.
These optimized AAD compounds meet the following requirements for an urgently needed new anthelmintic for livestock: low toxicity, favourable pharmacokinetic properties and broad-spectrum efficacy against sheep and cattle nematodes. Moreover, this efficacy includes multidrug-resistant parasites owing to a presumed activation of signalling. However, nematodes will ultimately develop resistance to any new drug, including the AADs. To secure the maximum lifespan of the AADs as well as the current anthelmintic drugs, monitoring of drug resistance and rational exploration of combinations with current or future drugs will be necessary. If the excellent tolerability of the AADs in ruminants can be proven for humans, the class may offer an alternative anthelmintic for human medical practice.

A new class of anthelmintics effective against drug-resistant nematodes
Nature 2008 452: 176-180

Evolution of root nodule symbiosis with nitrogen-fixing bacteria

Nitrogen is essential for all plants and animals, but despite being surrounded by an element that constitutes 79% of air, only a few bacteria can absorb it directly from the environment. All other species are ultimately dependent on these microbes as a source. A new paper in the open-access journal PLoS Biology investigates the genetics behind the symbiotic relationship between these nitrogen-fixing bacteria and plants, and presents evidence of specific genetic changes that might have led to the evolution of symbioses with nitrogen-fixing bacteria from a more ancient form of symbiosis.

About 80% of all land plants have a symbiotic relationship with fungi of the phylum Glomeromycota. The fungus penetrates cells in the plant s roots, and provides the plant with phosphates and other nutrients from the soil. This kind of symbiosis is called an arbuscular mycorrhiza, and evolved more than 400 million years ago. Professor Martin Parniske and colleagues started their study by looking at genes known to be involved in arbuscular mycorrhiza, to see whether they could find evidence of any specific genetic differences in plants that form symbioses also with nitrogen-fixing bacteria. In this so-called root nodule symbiosis bacteria live in the root cells of the host plants, where they bind elementary nitrogen from the air in special organs, the nodules. In return, the microbes get high-energy carbohydrates produced by photosynthesis in the host plant.

It had already been speculated that genes involved in the arbuscular mycorrhiza symbiosis might have been recruited for nodulation, as these symbioses both involve intracellular relationships. One clue was that several genes, including the so-called symbiosis-receptor-kinase-gene (SYMRK), are involved in a genetic program that links arbuscular mycorrhiza and one form of bacterial nodule symbiosis. This work is an important step towards understanding the evolution of nitrogen-fixation in plants, and even whether plants that don’t form symbioses with nitrogen-fixing bacteria could be engineered to do so, thus increasing their nutritional value.

Functional adaptation of a plant receptor-kinase paved the way for the evolution of intracellular root symbioses with bacteria. 2008 PLoS Biol 6 (3): e68.

E. coli O157:H7 - getting to the bottom of the burger bug

The Zoonotic and Animal Pathogens Research Laboratory at the University of Edinburgh has worked with a UK-based animation company to produce a full-length animation representing the key stages of E. coli O157:H7 interaction within the gastrointestinal tract. This movie was featured in the August 2004 issue of Microbiology Today, published by the Society for General Microbiology.

Resistance to Plant Viruses

Some estimates put total the worldwide economic damage due to plant viruses as high as US$60 billion per year, in addition to the human costs in terms of hunger and poverty. So understanding how viruses damage plants and how this can be avoided is of the utmost importance. There are hundreds of plant-pathogenic viruses, which cause a range of diseases. However, plants have evolved elaborate and effective defence mechanisms to prevent or limit virus damage. Plants contain resistance (R) genes, which allow resistance to a range of pathogens including viruses. Each R gene gives resistance to a particular pathogen. A number of R genes have been studied in detail (Mechanisms of plant resistance to viruses. 2005 Nature Reviews Microbiology 3: 789-798). Several molecules and signalling pathways are induced on pathogen recognition, and they cooperate to produce a defensive response. Some of the best characterized of these molecules include salicylic acid, nitric oxide and reactive oxygen species, in addition to some plant hormones. RNA silencing is a highly conserved pathway in animals and plants that functions in development and in the maintenance of genome integrity. Plants have adapted this system for antiviral defences, and of course, plant viruses have in turn developed mechanisms to suppress RNA silencing. Double-stranded RNA (dsRNA) is the trigger for RNA silencing. Most plant viruses (59 of the 80-odd plant virus genera) are RNA viruses and plants have several homologues of the DICER endonuclease. These enzymes generate siRNA (short interfering RNA) as an antiviral response. So these two pathways - RNA silencing and R-gene-mediated resistance - interact to produce an effective defence response in plants.

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Having penetrated the plant cell wall, the first defence mechanism which viruses encounter are extracellular surface receptors on the host cell plasma membrane that recognize pathogen-associated molecular patterns (PAMPs). This interaction initiates PAMP-triggered immunity (PTI), which sometimes halts infection before the virus gains a hold in the plant. However, plant viruses have evolved the means to suppress PTI by interfering with recognition at the plasma membrane. Effector-triggered immunity involves the direct or indirect recognition of the virus proteins used to subvert PTI by plant R proteins (Host-Microbe Interactions: Shaping the Evolution of the Plant Immune Response. 2006 Cell 124: 803-814). Virus virulence determinants suppress the host RNA silencing response.

Genetic engineering offers a means of incorporating new virus resistance traits into existing plant varieties. The initial attempts to create transgenes conferring virus resistance were based on the pathogen-derived resistance determinants, for example, the expression of virus coat protein genes in transgenic plants was shown to induce protective effects. Since then, a large variety of virus genes encoding structural and non-structural proteins has also been shown to confer resistance to disease (Strategies for antiviral resistance in transgenic plants. 2008 Molecular Plant Pathology 9: 73-83). Subsequently, non-coding virus RNAs have been shown to be a potential trigger for virus resistance in transgenic plants, which led to the discovery of RNA silencing.

Plants have evolved a robust innate immune system that exhibits striking similarities as well as significant differences with innate immunity in animals. For example, plants are capable of perceiving PAMPs through pattern recognition receptors that bear structural similarities to animal Toll-like receptors. In addition, plants have evolved a second surveillance system based on cytoplasmic “NB-LRR” proteins (nucleotide-binding, leucine-rich repeat) that are structurally similar to animal nucleotide-binding and oligomerization domain (NOD)-like receptors. Plant NB-LRR proteins do not detect PAMPs, but recognize proteins that viruses produce in plant cells. (Molecular diversity at the plant-pathogen interface. 2007 Dev Comp Immunol)

The number of different strategies that have been developed for creating virus and viroid resistance is one of the major success stories in biotechnology. However, few of these strategies have ever been taken past the proof of principle stage in the laboratory, or small-scale field trials. The only engineered virus-resistant plants that have been grown on a large commercial scale were transformed with complete virus transgenes, and it appears that the resistance induced is of the RNA silencing type in all these cases. That means that there is still enormous potential for overcoming the detrimental effects of plant viruses through genetic manipulation of valuable plant varieties.

Infectious diseases and extinction risk in wild mammals

Parasite-driven declines in wildlife have become increasingly common and can pose significant risks to natural populations. These authors used the IUCN Red List of Threatened and Endangered Species and compiled data on hosts threatened by infectious disease and their parasites to better understand the role of infectious disease in contemporary host extinctions. The majority of mammal species considered threatened by parasites were either carnivores or artiodactyls, two groups that include the majority of domesticated animals. Parasites affecting host threat status were predominantly viruses and bacteria that infect a wide range of host species, including domesticated animals. Counter to predictions, parasites transmitted by close contact were more likely to cause extinction risk than those transmitted by other routes. Mammal species threatened by parasites were not better studied for infectious diseases than other threatened mammals and did not have more parasites or differ in four key traits demonstrated to affect parasite species richness in other comparative studies. The findings underscore the need for better information concerning the distribution and impacts of infectious diseases in populations of endangered mammals.

Mammals from groups that are closely related to domesticated animals are at the greatest risk of parasite-mediated declines, most likely due to cross-species transmission of generalist viruses and bacteria. Efforts to provide a more comprehensive view of the role of parasites in wildlife extinction risk will require increased collaboration among wildlife ecologists, veterinary workers, and conservation organizations. Characteristics of threatening parasites highlight the possibility that future control strategies targeted at reducing cross-species transmission of high-risk parasites, either by vaccination or by limiting contact with domestic animals, may significantly reduce the risk of parasite-mediated wildlife declines.

Infectious diseases and extinction risk in wild mammals.
Conservation Biol. 2007 21: 1269-1279

Maybe Not Quite The End

This post is from regular guest blogger:

Ed Rybicki, Department of Molecular and Cell Biology, University of Cape Town, South Africa.

Given the current scare over H5N1 influenza virus in swans in the UK, it is possibly timely to recall that I wrote a little while ago in MicrobiologyBytes about how easy it appeared to be for the highly pathogenic H5N1 avian influenza virus to change receptor and therefore host specificity: all it apparently needed was substitutions at position 129 and 134 in the HA protein to change from binding avian-type sialic acid (SA) α2,3Gal(actose) receptors to the human-type SA α2,6Gal receptor. And the outlook was gloomy, and panic was close at hand.

Fortunately for us, it turns out that things are not so simple. According to a letter in the January 2008 issue of Nature Biotechnology, it is a characteristic structural topology, and not just the α2,6 linkage, that enables specific binding of HA to α2,6 sialylated glycans. The authors state:

…recognition of this topology may be critical for adaptation of HA to bind glycans in the upper respiratory tract of humans. An integrated biochemical, analytical and data mining approach demonstrates that HAs from the human-adapted H1N1 and H3N2 viruses, but not H5N1 (bird flu) viruses, specifically bind to long α2-6 sialylated glycans with this topology. This could explain why H5N1 viruses have not yet gained a foothold in the human population.

Apparently the critical shape in humans is umbrella-like, whereas the avian receptor is characteristically cone-like. Again from the paper:

The topology of α2-3 and α2-6 is governed by the glycosidic torsion angles of the trisaccharide motifs-Neu5Aca2-3Galb1-3/4GlcNAc and Neu5Aca2-6Galb1-4GlcNAc, respectively (Supplementary Fig. 3 online).

Ram Sasisekharan and colleagues showed that human-adapted viruses with mixed α2,3/α2,6 binding ability that bound the umbrella-type receptor were efficiently transmitted, whereas viruses with the same basic specificity that did not have HA binding specificity to “long” α2,6, were not.

This means that the perceived threat of H5N1 human adaptation and rapid spread has receded somewhat, as the virus HA needs considerably more adaptation than the simple mutations that were previously assumed to change the specificity. Furthermore, these findings also allow the possibility of using glycan arrays with long α2,6 molecules for the screening of H5N1 and other avian virus isolates for possible evolutionary adaptation to the appropriate receptor binding form. They close their paper with these encouraging words:

A sufficient understanding of the avian H5N1 HA mutations leading to long α2-6 binding specificity offers an opportunity for intervention through vaccine development to negate the eventuality of a H5N1 pandemic.

Now while I am happy that the threat may not be as imminent as I thought it was, I must point out that H5N1 flu is still one of the nastiest pandemic prospects facing humanity. The virus is established as an endemic pathogen worldwide, meaning it could break into the human population just about anywhere people keep domestic poultry. While the threat of mutation leading to rapid adaptation may be a lot less severe than we thought, there is still the possibility of
recombination / reassortment leading to a virulent, human-adapted virus - and we should recall that the flu pandemics of the 1950s and 1960s were due to reassortment between the prevailing H1N1 virus and a H2N2 type in 1957, and between a H3-containing virus and the prevailing H2N2 in 1968. And the contributing avian viruses were nowhere near as well distributed as H5N1 is now, nor as virulent …

So the apocalypse is still nigh - but possibly less nigh than we may have thought. However, as the inimitable Gregory House has observed, “It’s not paranoia if they’re really after you”. And I think they still are.

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Related:

• Influenza H5N1 in Dorset, UK
• This is the End
• H5N1 influenza is no longer “bird flu”
• Human Infections with Avian Influenza H5N1 Viruses

Flexiviridae: A case study in virion and genome plasticity

The plant virus family Flexiviridae includes the definitive genera Potexvirus, Mandarivirus, Allexivirus, Carlavirus, Foveavirus, Capillovirus, Vitivirus, Trichovirus, the putative genus Citrivirus, and some unassigned species. Its establishment was based on similarities in virion morphology, common features in genome type and organization, and strong phylogenetic relationships between replicational and structural proteins. In this review, the authors provide a brief account of the main biological and molecular properties of the members of the family, with special emphasis on the relationships within and among the genera. In phylogenetic analyses the Potexvirus-like replicases were more closely related to tymoviruses than to carlaviruses. The authors postulate a common evolutionary ancestor for the family Tymoviridae and the two distinct evolutionary clusters of the Flexiviridae, i.e. a plant virus with a polyadenylated genome, filamentous virions, and a triple gene block of movement proteins. Subsequent recombination and gene loss would then have generated a very diverse group of plant and fungal viruses.
The most prominent aspect of the Flexiviridae is the unusual fluidity of their genomes compared to those of the related rod-shaped or icosahedral RNA viruses of the alphavirus-like superfamily. This could be explained by the relative ease with which the filamentous virions can accommodate the increase or reduction in the size of the viral genome. There is no region of flexiviral genomes that is left untouched by genetic variation. Do flexiviruses benefit from their genetic plasticity? It seems that the answer is yes.

Family Flexiviridae: A Case Study in Virion and Genome Plasticity
Annual Review of Phytopathology 2007 45: 73-100