MicrobiologyBytes

Acute respiratory viruses cause substantial morbidity and mortality worldwide. Lower respiratory-tract infections are the leading cause of communicable disease death and among the top five contributors to disability-adjusted life years. Viruses are the primary cause of lower respiratory-tract infections in children and a substantial cause of such infections in all age-groups. The incubation period of an infectious disease is the time between infection and symptom onset. This period is widely reported because it is useful in infectious disease surveillance and control, in which the time of symptom onset may be the only indication of the time of infection. The incubation period plays an essential part in surveillance for healthcare-associated infections, and may aid in diagnosis if laboratory facilities are unavailable. The incubation period is clinically relevant in the administration of antiviral medications, many of which are most effective when given before or immediately after symptom onset. Epidemiological studies depend on the incubation period to identify potential sources of infection. Predictive models designed to inform policy decisions use the incubation period to evaluate the potential of surveillance programmes and interventions to confront emerging epidemics.

The length of the incubation period by comparison with the latent period (the time between infection and becoming infectious) determines the potential effectiveness of control measures that target symptomatic individuals. “4–5 days” may refer to the most common range, the highest and lowest incubation periods in a study, or some other interval. Without knowing which summary measure is being stated, it is hard to use this information to make clinical or infection control decisions. Estimates given without attribution or based on few observations do not meet the standards of evidence we demand for modern medical information. A recent paper reviews the literature on nine respiratory viruses selected for their clinical or public-health importance: adenovirus, human coronavirus, SARS-associated coronavirus, influenza, measles, human metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), and rhinovirus. By systematic review and analysis of published estimates and data, the authors aimed to capture the consensus in the medical literature on these incubation periods, characterise the evidence underlying this consensus, and provide improved estimates of incubation periods for these infections.

Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis 2009;
9: 291–300
Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.

Related:

• One virus particle can be enough to cause infection
• Adenoviruses
• SARS Virus May Be Tough To Beat

A biofilm is a surface-associated population of microbes that is embedded in a cement of extracellular compounds. This cement is known as matrix. The two main functions of matrix are to protect cells from their surrounding environment, preventing drugs and other stresses from penetrating the biofilm, and to maintain the architectural stability of the biofilm, acting as a glue to hold the cells together. The presence of matrix is a contributing factor to the high degree of resistance to antimicrobial drugs observed in biofilms. Because biofilms have a major impact on human health, and because matrix is such a pivotal component of biofilms, it is important to understand how the production of matrix is regulated.

A group of researchers has identified a novel regulatory gene network that plays an important role in the spread of common, and sometimes deadly, fungus infections. The new findings establish the role of Zap1 protein in the activation of genes that regulate the synthesis of biofilm matrix. Candida albicans is a fungus, more specifically a yeast, which approximately 80 percent of people have in their gastrointestinal and genitourinary tract with no ill effects. However, at elevated levels it can cause non-life threatening conditions like thrush and yeast infections. C. albicans infection becomes much more serious, and can be lethal in those with compromised immune systems who have an implantable medical device such as a pacemaker or artificial joint, or who use broad-spectrum antibiotics. Central to such infections is the biofilm –  a population of microbes, in this case C. albicans cells, joined together to form a sheet of cells. The cells in the biofilm produce extracellular components such as proteins and sugars, which form a cement-like matrix. This matrix serves to protect the cells of the biofilm, preventing drugs and other stressors from attacking the cells while acting as a glue that holds the cells together. By doing this, the matrix provides an environment in which yeast cells in the biofilm can thrive, promoting infection and drug resistance.

Biofilms have a major impact on human health and matrix is such a pivotal component of biofilms. It is important to understand how the production of matrix is regulated. In the study, the scientists found that the zinc-responsive regulatory protein Zap1 prevents the production of soluble beta-1,3 glucan, a sugar that is a major component of matrix. They also identified other genes whose expression is controlled by Zap1, called Zap1 target genes. They found that these genes encode two types of enzymes, glucoamylases and alcohol dehydrogenases, which both govern the production and maturation of matrix components. Understanding this novel regulatory gene network gives us insight into the metabolic processes that contribute to biofilm formation, and the role the network plays in infection. By better understanding the mechanisms by which biofilms develop and grow, we can start to look at targets for combating infection.

Biofilm Matrix Regulation by Candida albicans Zap1. 2009 PLoS Biol 7(6): e1000133 doi:10.1371/journal.pbio.1000133
A biofilm is a surface-associated population of microorganisms embedded in a matrix of extracellular polymeric substances. Biofilms are a major natural growth form of microorganisms and the cause of pervasive device-associated infection. This report focuses on the biofilm matrix of Candida albicans, the major fungal pathogen of humans. We report here that the C. albicans zinc-response transcription factor Zap1 is a negative regulator of a major matrix component, soluble b-1,3 glucan, in both in vitro and in vivo biofilm models. To understand the mechanistic relationship between Zap1 and matrix, we identified Zap1 target genes through expression profiling and full genome chromatin immunoprecipitation. On the basis of these results, we designed additional experiments showing that two glucoamylases, Gca1 and Gca2, have positive roles in matrix production and may function through hydrolysis of insoluble b-1,3 glucan chains. We also show that a group of alcohol dehydrogenases Adh5, Csh1, and Ifd6 have roles in matrix production: Adh5 acts positively, and Csh1 and Ifd6, negatively. We propose that these alcohol dehydrogenases generate quorum-sensing aryl and acyl alcohols that in turn govern multiple events in biofilm maturation. Our findings define a novel regulatory circuit and its mechanism of control of a process central to infection.

Related:

• Candida albicans: the video
• Candida parapsilosis secreted lipase is a major virulence factor
• Bugs Against Biofilms

Wild waterfowl and seabirds are major natural reservoirs of influenza A viruses. Genetic analysis has revealed that influenza A viruses found in all other host species, including humans, were ultimately derived from avian viruses. Geographical separation of host species has shaped the influenza gene pool into largely independently evolving Eurasian and American lineages, although some gene flow between these regions has been documented.

Reassortment between Eurasian and North American lineage viruses have also been documented in wild aquatic bird populations indicating that in these two geographically segregated lineages there is some mixing of viruses. However, the possible effects of virus gene flow between the Eurasian and American gene pools on influenza virus evolution and population structure had not been fully explored until recently. A new study shows that virus gene flow from Eurasia has led to the exclusion of some viruses from North America, most likely mediated by competition for susceptible hosts (Gene flow and competitive exclusion of avian influenza A virus in natural reservoir hosts. Virology, 5 June 2009 doi:10.1016/j.virol.2009.05.002).

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The researchers found that intercontinental gene flow is frequently mediated through seabirds, highlighting the need for increased surveillance of influenza viruses in a broader spectrum of potential host species. Such selection is only likely to occur in cases where the viruses in question are sufficiently antigenically similar to induce a cross-protective immune response.

Population genetics offers a number of concepts and principles to explain the evolutionary behavior of RNA viruses. For example, the competitive exclusion principle states that when two species compete for limited resources one species will eventually outcompete the other and become dominant. In the case of RNA viruses, a combination of high replication numbers and high nucleotide substitution rates makes the prolonged co-existence of two or more genetically distinct virus populations unlikely. In theory, the competitive pressure exerted by an invading influenza virus will select for viruses with increased reproduction and transmissibility. Therefore the adaptive advantage conferred through competition may contribute to influenza disease emergence.

Increased genome surveillance of influenza viruses in bird populations is critical for understanding the effects of gene flow between populations. The extent of virus competition in avian populations infected with influenza remains unknown. In Asia, the long-term endemicity of H5N1 influenza appears to have replaced, most probably through competitive selection, low pathogenic H5 subtype viruses that have been only rarely isolated from poultry in Asia since 2000 when compared to previous surveillance in the 1970′s. This new work provides a possible mechanism for disease emergence and transmission from natural reservoir hosts.

Related:

• The Biology of Influenza
• How influenza pandemics get started

The PLoS ONE Prokaryotic Genome Collection is an attempt to present and highlight a number of important articles that describe whole genome sequence and/or comparative genomics of important prokaryotic organisms:

A Flood of Microbial Genomes – Do We Need More?
Complete genome sequences of important bacterial pathogens and industrial organisms hold significant consequences and opportunities for human health, industry and the environment. Addressing biological and clinical problems through genome sequence based approaches offers many commercial opportunities. The aftermath of whole genome sequencing has revealed new insights into evolution of bacterial lifestyles including strategies for adaptation to new niches and overcoming competitors. Whole genome sequences representing more than 1500 prokaryotic organisms combined with the dozens (to hundreds) of strain re-sequencing projects are posing mind boggling problems on the optimal utilization of the resultant ‘omic’ datasets. Consequently, microbiologists are confronted with the challenge to translate these data into better human and animal healthcare solutions and pursue basic research approaches to interpret the data in ecological and evolutionary perspectives. New informatic approaches towards optimal utilization, holistic integration and meaningful interpretation of the genome sequence data are extremely necessary.

Related:

• Global functional atlas of Escherichia coli proteins

A cockatrice was a flamboyant sight at medieval banquets, featuring a roasted chimera of rooster fused to a suckling pig. In this article in Microbiology Today (pdf) Ed Bolt and Stephane Delmas suggest that there are similarities with archaea, ancient micro-organisms that have features of both bacteria and eukaryotes within their genomes:

Archaea and bacteria are micro-organisms that are similar, yet different. Archaea are evolutionarily ancient organisms that have soaked up diverse ecosystems for at least 2.5 billion years. They are, like bacteria, unencumbered by various complex sub-cellular structures (e.g. mitochondria, a membrane-bound nucleus) and as such have been for most of their long existence, or at least from when microbiologists started looking at them, considered to be bacteria that had evolved to thrive in extreme environments (e.g. at high temperature or salinity). For this reason they were often called archeabacteria. However, DNA sequencing experiments in the 1970s drove a wedge through the bacteria, splitting it into two separate domains of cellular life: the Bacteria and the Archaea. The genetic distinction between bacteria and archaea is now generally accepted since its original proposal in 1977, but has its evolutionary root much earlier, probably pre-dating the emergence of oxygen 2.5 billion years ago. Therefore, the classification of cellular organisms is now usually represented in a tree of life consisting of three domains, Bacteria, Archaea and Eukarya.

Read more

Related:

• Unique cell division machinery in the Archaea

Tick-borne encephalitis virus is a Flavivirus, and the causative agent of tick-borne encephalitis (TBE), a potentially fatal neurological infection affecting humans in Europe and Asia. From 1974 to 2003, a 400% increase in TBE morbidity has been observed in Europe, and TBEV can now be found in regions that were previously unaffected. TBE is now a notifiable disease in 16 European countries, and cases have been confirmed in areas where it has not been previously reported, for example Norway. Between 1990 and 2007 there were an average of 8,755 reported cases of TBE per year in Europe and Russia, in comparison to an average of 2,755 per year between 1976 and 1989. This increase may have been caused by an expanding tick population, promoted by factors including climate change, social and political changes, and changes in land use.

Tick-borne Encephalitis Virus – a Review of an Emerging Zoonosis. J Gen Virol. May 6 2009
During the last thirty years, there has been a continued increase in human cases of tick-borne encephalitis (TBE) in Europe, a disease caused by Tick-borne encephalitis virus (TBEV). TBEV is endemic in an area ranging from Northern China and Japan, through Far-eastern Russia, to Europe, and is maintained in cycles involving Ixodid ticks (Ixodes ricinus and Ixodes persulcatus) and wild vertebrate hosts. The virus causes a potentially fatal neurological infection, with thousands of cases reported annually throughout Europe. TBE has a significant mortality rate depending upon the strain of virus, or may cause long-term neurological/neuropsychiatric sequelae in people affected. In this review, we comprehensively review TBEV, its epidemiology and pathogenesis, the clinical manifestations of TBE, along with vaccination and prevention. We also discuss the factors which may have influenced an apparent increase in the number of reported human cases each year, despite the availability of effective vaccines.

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• MicrobiologyBytes: Emerging Diseases
• Pathogenic Flaviviruses
• Extreme Weather Events And Epidemics

All scientific papers are important, but some are more important than others. Aside from its scientific importance, this paper is particularly important to me in purely personal terms. It comes from my own department. Ben Maddison was a PhD student in my laboratory many years ago and now heads up his own research group within the department. It’s also one of the final papers to come from Gary Whitelam, my former head of department, who died tragically last year. And as if all that wasn’t enough, as the UK starts to forget about how close we came to disaster with BSE, we’re still not completely sure that it’s all over.

Using the cutting-edge research technique of serial protein misfolding cyclic amplification (sPMCA), my colleagues show that prions are secreted in the milk from scrapie-exposed sheep. The sPMCA method involves incubating a small amount of abnormal prion with an excess of normal prion protein, so that some conversion takes place. The growing chain of misfolded protein is then blasted with ultrasound, breaking it down into smaller chains and so rapidly increasing the amount of abnormal protein available to cause conversions. By repeating the cycle, the mass of normal protein is rapidly changed into misfolded prion.

Since scrapie is not transmissible to humans, these findings do not indicate the likely introduction of zoonotic prions from sheep into the human food chain. Nevertheless, the data do indicate caution in the risk assessment associated with such foods. Although it is unknown if analogous shedding of prions into milk occurs with bovine BSE, evidence from previous epidemiological and bioassay studies suggests that such a scenario seems unlikely to cause clinical disease. However, the present report strongly suggests that given the importance of cow’s milk in the human diet the potential presence of low levels of prions within milk warrants further investigation. Analyzing milk samples by sPMCA offers a methodology with clear potential for the identification of clinically sick animals and those with preclinical/subclinical prion disease. Such a non-invasive, live animal assay has the potential to contribute to the epidemiological study, management and control of prion diseases within farmed animals.

Prions are secreted in milk from clinically normal scrapie-exposed sheep. J Virol. Jun 3 2009. doi:10.1128/JVI.00051-09
The potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. Here, serial protein misfolding cyclic amplification (sPMCA) allowed the detection of prions in milk from clinically-affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset, irrespective of the immunohistochemical detection of protease-resistant PrP(Sc) within lymphoreticular and CNS tissues. These data indicate the secretion of prions within milk during the early stages of disease progression and a role for milk in prion transmission. Furthermore, the application of sPMCA to milk samples offers a non-invasive methodology to detect scrapie during preclinical/subclinical disease.

Related:

• Prions in Milk
• The Origin of BSE
• What the heck are prions for?
• Fears over new wave of vCJD deaths

The panspermia (“seeds everywhere”) theory says that life could originate anywhere in the universe where conditions are favorable, and that mechanisms exist for the movement of lifeforms through space. The abundant life on Earth need not have originated here. Scientific thinking about panspermia began to gain impetus in the 19th century after chemists reported finding organic compounds in samples of meteorites from space. The notion that these carbonaceous materials represented living matter inspired the German doctor H.E. Richter to propose a mechanism for panspermia, in which meteorites glancing a planet’s atmosphere at a very shallow angle could acquire atmospheric microorganisms before skipping back into space.

Richter’s idea of meteors as the transfer vehicles for life through space was expanded on by two of the leading physicists, von Helmholtz and William Thomson (Lord Kelvin). In 1871, each proposed a hypothesis that outlined many details of what has since become known as lithopanspermia based on cosmic impacts. Thomson proposed that space bodies hitting a living planet like Earth could blast life-bearing rocks into space, and that similar meteorites blasted off other living worlds may have inoculated the early Earth with life. In addition to meteorites, von Helmholtz included comets as possible vehicles and proposed an important test – that organisms arising from the donor and recipient planets would share a common ancestry.

In the mid-20th century, Hoyle and Wickramasinghe proposed a cyclical version of panspermia, in which they postulated that interstellar dust grains were actually viable microorganisms that were amplified in the “warm, wet interiors” of comets, then delivered to planets by cometary impacts. According to this theory, after further amplification on the planets, the resulting viable biological material was then returned to interstellar space to start the cycle again.

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Almost from the outset, the lithopanspermia hypothesis drew intense criticism – at the time it was thought that living organisms could not possibly survive ejection by impact, transit through space and entry onto another planet. These views held sway until the discovery on Earth and characterization of meteorites from Mars in the late 20th century.

Considerable experimental effort has been expended in constructing simulations of various aspects of lithopanspermia and measuring the survival of microorganisms to conditions approximating those during the process. Because of their intrinsic high resistance to a variety of environmental stresses and ease of cultivation, spores of Bacillus spp. (in particular B. subtilis) are the most widely-used model microorganism for lithopanspermia studies. However, various other model microorganisms have been utilized in such simulations, such as the soil bacterium Deinococcus radiodurans.

One of the main arguments against lithopanspermia is that the energy required to eject rocks from the surface of a planet into space would be so high as to melt or even vaporize the rock, rendering it sterile. However, since the late 1970s it has been recognized that some meteorites found on Earth are actually bits of crust derived from the Moon and Mars, and had never heated above 100°C.

Current results suggest that most terrestrial microbes tested to date would encounter severe difficulties surviving and growing in the present-day Martian surface environment. The logical extension of this reasoning is that Martian microorganisms might also have a difficult time prospering in today’s Earth environment. It must be kept in mind, however, that we have not yet completely defined the extreme limits of life on Earth. In addition, we have only just begun to scratch the surface of Mars in search of habitable conditions and evidence of past or present life. There is still a long journey ahead. Fancy being the first microbiologist on Mars?

Related:

• Ancient micronauts: interplanetary transport of microbes by cosmic impacts. Trends Microbiol. May 21 2009
• Bugs in space
• Is microbial life on Mars possible?
• Life on Mars?

Honey bee colonies are in decline in many parts of the world, in part due to pressures from a diverse assemblage of parasites and pathogens. Scientists have sequenced the genome of a parasite that can kill honey bees. Nosema ceranae is one of many pathogens suspected of contributing to the current bee population decline, termed colony collapse disorder (CCD). In 2006, CCD began devastating commercial beekeeping operations, with some beekeepers reporting losses of up to 90 percent, according to the USDA. Researchers believe CCD may be the result of a combination of pathogens, parasites and stress factors, but the cause remains elusive. At stake are honey bees that play a valuable part in a $15 billion industry of crop farming in the United States.

The microsporidian Nosema is a fungus-related microbe that produces spores that bees consume when they forage. Infection spreads from their digestive tract to other tissues. Within weeks, colonies are either wiped out or lose much of their strength. Nosema apis was the leading cause of microsporidia infections among domestic bee colonies until recently when N. ceranae jumped from Asian honey bees to the European honey bees used commercially in the United States. Sequencing the genome should help scientists trace the parasite’s migration patterns, determine how it became dominant, and help resolve the spread of infection by enabling the development of diagnostic tests and treatments.

N. ceranae has an extremely reduced and AT-biased genome, yet one with substantial numbers of repetitive elements. The sequence identifies novel genes that appear to be conserved among microsporidia but undetected outside this phylum, which are of special interest as potential virulence factors for these obligate pathogens. A previously unrecognized motif is found upstream of many start codons and likely plays a role in gene regulation across the microsporidia. These and other comparisons provide insight into the architecture, regulation, and evolution of microsporidian genomes, and provide the first genetic tools for understanding how this pathogen interacts with honey bee hosts.

Genomic Analyses of the Microsporidian Nosema ceranae, an Emergent Pathogen of Honey Bees. PLoS Pathog 5(6): e1000466. doi:10.1371/journal.ppat.1000466
Recent steep declines in honey bee health have severely impacted the beekeeping industry, presenting new risks for agricultural commodities that depend on insect pollination. Honey bee declines could reflect increased pressures from parasites and pathogens. The incidence of the microsporidian pathogen Nosema ceranae has increased significantly in the past decade. Here we present a draft assembly (7.86 MB) of the N. ceranae genome derived from pyrosequence data, including initial gene models and genomic comparisons with other members of this highly derived fungal lineage. N. ceranae has a strongly AT-biased genome (74% A+T) and a diversity of repetitive elements, complicating the assembly. Of 2,614 predicted protein-coding sequences, we conservatively estimate that 1,366 have homologs in the microsporidian Encephalitozoon cuniculi, the most closely related published genome sequence. We identify genes conserved among microsporidia that lack clear homology outside this group, which are of special interest as potential virulence factors in this group of obligate parasites. A substantial fraction of the diminutive N. ceranae proteome consists of novel and transposable element proteins. For a majority of well-supported gene models, a conserved sense-strand motif can be found within 15 bases upstream of the start codon; a previously uncharacterized version of this motif is also present in E. cuniculi. These comparisons provide insight into the architecture, regulation, and evolution of microsporidian genomes, and will drive investigations into honey bee–Nosema interactions.

Related:

• Colony Collapse Disorder
• The great bee swindle – colony collapse disorder
• To bee or not to bee