MicrobiologyBytes

Amphibians such as frogs and toads are being driven to extinction by an aquatic fungus. This microbe, commonly called Bd, is spreading rapidly around the world and contributing to the decline in the biodiversity of the animals. In this article in Microbiology Today (pdf) Matthew Fisher believes that if control measures are not implemented, one-third of amphibian species could disappear:

Amphibians became the most ancient class of land-dwelling vertebrates when, 360 million years ago, Ichthyostega first hauled itself onto what was then Greenland. Since then, the amphibia have diversified into over 6,300 species that not only settled all continents except Antarctica, but also survived the catastrophic extinction events that overwhelmed their sister group, the dinosaurs. However, longevity of species is no guarantee of their future success; modern-day amphibians are suffering rates of extinction that far exceed those of any other class of vertebrates, including mammals and birds. Nearly one-third of amphibian species are threatened. The question of why amphibians are becoming extinct at these accelerated rates has puzzled scientists for three decades. While it is now clear that we are heading for a new anthropocene mass-extinction event as a consequence of human-driven planetary degradation, it has not been clear why this should be affecting amphibians more than other taxa. Further, many amphibian declines and extinctions were observed to occur in pristine environments that are relatively untouched by humans, such as rainforests and montane systems. A clue to the mystery came about when scientists working in Central America noted that the declines in amphibian biodiversity appeared to be occurring in a wave-like manner, with the initial losses being observed in Costa Rica, then spreading southwards towards the Panama Canal at rates of up to 43 km per year. These patterns of decline were suggestive of an epidemic, spreading pathogen, and in 1997 an international team of scientists discovered a new organism that appeared to be associated with many previously ‘enigmatic’ amphibian extinctions in two regions: Central America and north-eastern Australia. In 1999, the mycologist Joyce Longcore formally described this organism as new species of aquatic fungus and named it Batrachochytrium dendrobatidis.

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Cholera, a severe form of acute secretory diarrhoea, is caused by the gamma-proteobacterium Vibrio cholerae. Pathogenic strains harbour a cholera toxin prophage (CTXΦ) that carries the genes that encode the cholera toxin (CT), a key virulence factor that is directly responsible for the major clinical symptoms of the disease. CT binds to a specific receptor (GM1) on host enterocytes and is internalized, leading to elevated intracellular cAMP levels and resulting in a major loss of water and electrolytes in profuse secretory diarrhoea. To date, >200 serogroups (a sub-species taxonomic classification) of V. cholerae have been identified, based on variations in O-antigen structure. Most of the clinical strains belonging to serogroups O1 and O139 are toxigenic, and are responsible for all the major cholera epidemics and pandemics on record. Conversely, strains belonging to other serogroups (collectively known as ‘non-O1/non-O139’) are rarely toxigenic (<1%) and have seldom caused epidemics. Therefore, it appears that the ability to produce CT is essential if the disease is to result in major cholera epidemics.

Evolution of new variants of Vibrio cholerae O1. Trends Microbiol. Nov 24 2009
Vibrio cholerae typically contains a prophage that carries the genes encoding the cholera toxin, which is responsible for the major clinical symptoms of the disease. In recent years, new pathogenic variants of V. cholerae have emerged and spread throughout many Asian and African countries. These variants display a mixture of phenotypic and genotypic traits from the two main biotypes (known as ‘classical’ and ‘El Tor’), suggesting that they are genetic hybrids. Classical and El Tor biotypes have been the most epidemiologically successful cholera strains during the past century, and it is believed that the new variants (which we call here ‘atypical El Tor’) are likely to develop successfully in a manner similar to these biotypes. Here, we describe recent advances in our understanding of the epidemiology and evolution of the atypical El Tor strains.

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• Cracking the cholera code
• Bacterial toxins

Prophylactic human papillomavirus (HPV) L1 virus like particle (VLP) vaccines have been shown, in large randomized controlled clinical trials, to be very immunogenic, well tolerated and highly efficacious against ano-genital disease caused by the vaccine HPV types. However, these vaccines, at the present, protect against only two of the 15 oncogenic genital HPV types, they are expensive, delivered by intramuscular injection and require a cold chain. The challenges are to develop cheap, thermostable vaccines that can be delivered by noninjectable methods that provide long-term (decades) protection at mucosal surfaces to most, if not all, oncogenic HPV types that is as good as the current VLP vaccines. Polyvalent VLP vaccines covering several oncogenic types are in clinical trials. The most promising of the non-VLP second generation vaccines include L1 capsomers and L2 protein and peptides, suitably adjuvanted. Recent data on the mechanism of viral entry and the dynamics of the interaction of the viral capsid proteins L1 and L2 with the cell surface provide a rationale for the protection offered by these new approaches. These second generation vaccines are immunogenic and can provide broad protection but are either at early stage in clinical trial or not in trials. The current VLP prophylactic vaccines are likely to be the only option for the coming decade.

Prospects for new human papillomavirus vaccines. Curr Opin Infect Dis. Nov 18 2009

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Chagas disease, caused by the parasite Trypanosoma cruzi, transmitted to humans by blood-feeding insects, infects an estimated 8 to 11 million people throughout Mexico, and Central and South America. Although it is still rare in the United States, according to the Centers for Disease Control and Prevention (CDC), there are 300,000 people with Chagas disease living in the United States, most of whom acquired the disease while living in other countries. The acute phase of Chagas’ disease can result in fever or swelling at the site of the insect bite, but many people do not experience symptoms at all. If left untreated, the disease enters an indeterminate phase in which no symptoms are present. During this phase, many people are not aware that they are infected, but approximately 30 percent will eventually develop life-threatening complications of the disease, including enlargement of the digestive tract and/or heart.

T. cruzi will go to great lengths to evade death once it has infected human host cells, researchers have discovered. In a new study, researchers describe how a protein called parasite-derived neurotrophic factor (PDNF) prolongs the life of the T. cruzi parasite by activating anti-apoptotic (or anti-cell-death) molecules in the host cell. These protective mechanisms help to explain how host cells continue to survive despite being exploited by T. cruzi parasites. How is it possible that the host cells stay alive for so long with thousands of T. cruzi parasites consuming the host cell’s vital resources? PDNF on the surface of T. cruzi inhibits cell death signals and activates cell-protective mechanisms, ensuring the parasite sufficient time to develop and reproduce in the host cell. Taking a multi-faceted approach, the researchers used bioinformatics, immunochemistry, intracellular colocalization microscopy, and in vitro enzymatic techniques to study T. cruzi’s survival in the host. This demonstrated that PDNF is a substrate and activator of Akt kinase, an enzyme that promotes cell survival by inhibiting cell death (apoptosis) proteins. Akt is a key regulator of diverse cellular processes, and supports cell survival not only by inhibiting apoptotic molecules, but additionally by increasing nutrient uptake and metabolism. If we can fully understand the mechanisms behind this protection, we can begin to explore ways to undermine it with treatment.

Trypanosoma cruzi targets Akt in host cells as an intracellular antiapoptotic strategy. 2009 Science Signalling, 2 (97) ra74. doi:10.1126/scisignal.2000374
The parasite Trypanosoma cruzi, which causes Chagas disease, differentiates in the cytosol of its host cell and then replicates and spreads infection, processes that require the long-term survival of the infected cells. Here, we show that in the cytosol, parasite-derived neurotrophic factor (PDNF), a trans-sialidase that is located on the surface of T. cruzi, is both a substrate and an activator of the serine-threonine kinase Akt, an antiapoptotic molecule. PDNF increases the expression of the gene that encodes Akt while suppressing the transcription of genes that encode proapoptotic factors. Consequently, PDNF elicits a sustained functional response that protects host cells from apoptosis induced by oxidative stress and the proinflammatory cytokines tumor necrosis factor–alpha and transforming growth factor–beta. Given that PDNF also activates Akt by binding to the neurotrophic surface receptor TrkA, we propose that this protein activates survival signaling both at the cell surface, by acting as a receptor-binding ligand, and inside cells, by acting as a scaffolding adaptor protein downstream of the receptor.

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Research published this week in PLoS Medicine presents the most accurate assessment to date of the severity of the swine flu (H1N1) pandemic in the US. Scientists need to measure the severity of swine flu (how often infection with the swine flu virus results in symptoms leading to illness, hospitalization or death) so that appropriate pandemic plans can be put into place. Severity of swine flu has been difficult to measure for two main reasons: first, people with severe influenza are more likely than those with mild cases to seek care, making it difficult to estimate how many total cases have occurred, and second, the sheer number of cases means that recording routine case data can be difficult due to overburdening of public health systems. In this study, researchers from from Milwaukee (where all medically attended cases were recorded, whether hospitalized or not) and New York City (where only hospitalizations, intensive care admission and deaths were recorded, and a telephone survey of flu-like illness was conducted), along with earlier results from studies by the US CDC, used a statistical approach called Bayesian evidence synthesis. This enabled accurate estimations of severity to be made. Their analyses reveal that the autumn-winter pandemic wave of swine flu should have a death toll only slightly higher than, or considerably lower than, that caused by seasonal influenza in an average year, provided swine flu continues to behave as it did during the summer. Seasonal influenza mainly kills elderly adults, but the authors reveal that most deaths from swine flu will occur in non-elderly adults, a shift in age distribution that has been seen in previous pandemics.

The Severity of Pandemic H1N1 Influenza in the United States, from April to July 2009: A bayesian Analysis. PLoS Med 6(12): e1000207 doi:10.1371/journal.pmed.1000207
Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data – medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York – were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%–0.096%), sCIR of 0.239% (0.134%–0.458%), and sCHR of 1.44% (0.83%–2.64%). Using self-reported ILI, we obtained estimates approximately 7–96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5–17 y. sCHR appears to be lowest in persons aged 5–17; our data were too sparse to allow us to determine the group in which it was the highest. These estimates suggest that an autumn–winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0–4 and adults 18–64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.

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The popularity of functional foods is growing with health-conscious people, with many products available on the supermarket shelves. Prebiotics and probiotics may improve gut function in humans. In this article in Microbiology Today (pdf) Bob Rastall explores the potential benefits of including these compounds in the diet of cats and dogs:

Traditionally, human functional foods for gut health have been based on the probiotic concept. Probiotics are live bacterial supplements or food ingredients which, when taken in sufficient numbers, confer health benefits to the host. There are very many well-designed studies showing positive effects with probiotics, although some have not shown an effect. Probiotics have also been applied to pets, and bacterial species from the lactobacilli, bifidobacteria and enterococci are finding their way into pet foods. One big disadvantage with probiotics, however, is the need to keep the organisms viable in order to produce the full range of potential benefits. This is overcome in the human food industry by the use of chilled, usually dairy, products as delivery vehicles, an approach that is not very practical for pet food.

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XVIVO has created a nice animation of influenza virus replication. There are a few small points which are not strictly accurate, but overall, this gives very good impression of the processes which go on which cells are infected with influenza virus.

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National Standard Methods (NSMs) and are used widely throughout diagnostic microbiology and virology laboratories in both the UK and abroad. Each document is scrutinised when drafted by undergoing an open consultation and is also presented with comments received to National Standard Methods Working Group members at meetings. These working groups consist of biomedical scientists, clinical scientists, consultants and representatives from various organisations, e.g. Association of Medical Microbiologists, all of whom make valuable contributions to the documents. In addition each document is reviewed every three years when any relevant information is incorporated, the references are assessed for suitability and a horizon scan for new literature is carried out. All amendments are again scrutinised by over 1400 password holders and the working group members.

Each NSM not only contains information regarding the gold standard for methodology but also has a detailed introduction that provides the reader with knowledge regarding the infection, organism and origins. These documents are a valuable resource for clinical scientists, biomedical scientists and specialist registrars when preparing for exams and assessments. The documents may also be used as a teaching tool by critically reviewed during tutorials. We therefore believe that these documents will serve a dual purpose for your students. The NSMs are available for free via the HPA Standards website. A free password is required to access the documents and can be obtained by contacting the HPA Standards Unit at standards@hpa.org.uk.

Bacteria were once viewed as amorphous reaction vessels with chromosomes that wandered freely and randomly throughout the cell. The advent of genetically encoded fluorescent reporters harnessed to powerful cell-imaging technologies has enabled in vivo tracking of protein movement and revealed a strikingly complex inner world within bacteria. This inner environment is exquisitely organized, in a highly controlled state of flux, and responsive to changing functions demanded of the cell. For example, some proteins oscillate rapidly from one end of the cell to the other, whereas others form dynamic helices along the length of the cell or rings across its midsection, and yet others form distributed focal complexes on the cell’s surface or clusters at specific intracellular sites. Processes controlled at multiple levels construct (and remove) subsystems and surface structures at specific times and places in response to internal and external signals. This dynamic internal architecture facilitates behaviors as diverse as symmetric and asymmetric division, motility, chemotaxis, morphological differentiation, assembly into multicellular communities, and interactions with animal and plant hosts.

Despite their small size, bacteria have a remarkably intricate internal organization. Bacteria deploy proteins and protein complexes to particular locations and do so in a dynamic manner in lockstep with the organized deployment of their chromosome. The dynamic subcellular localization of protein complexes is an integral feature of regulatory processes of bacterial cells. This review article explores why bacteria dynamically deploy key regulatory proteins to particular sites in the cell and how this positioning and repositioning is achieved.

Why and How Bacteria Localize Proteins. Science 326: 1225-1228, 27 November 2009. doi:10.1126/science.1175685

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