MicrobiologyBytes

Lentiviruses owe their name (lenti means slow in latin) to the long period of time elapsing between the initial infection and the onset of the disease, that can protract over a period of months or even years. Viruses belonging to the Lentivirus genus are present in primates, ungulates (horse, cattle, sheep and goat) and felids (cat). Primates are the natural host for several lineages of closely related simian and human immunodeficiency viruses (SIV and HIV) that are the causative agents of acquired immunodeficiency syndrome (AIDS).

Lentivirus vectors bears an obvious advantage over other retrovirus vectors in that they offer the possibility to efficiently target non-dividing and differentiated cells, such as neurons. Paradoxically, the use of retrovirus vectors is hindered by the same process that makes them interesting for gene therapy, i.e., integration. This process is largely nonspecific and, as it has been shown in vivo, may either be of no consequence to the cell or lead to serious drawbacks. Although this problem may in theory be minimized in gene therapy applications targeting terminally differentiated cells, the problem of integration is serious. To this end, a number of alternative strategies have been developed, ranging from the redirection of retrovirus integration to particular chromosomal locations, to the ablation of the integration process altogether. Although in its infancy, the efforts to redirect retrovirus integration must be pursued and researchers may possibly transpose to lentiviruses a mechanism of specific integration used by other viruses.

The Inside Out of Lentiviral Vectors. (2011) Viruses 3(2): 132-159; doi:10.3390/v3020132
Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them.

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• Retroviruses
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• Why is HIV a pathogen?

Chemists and engineers taught us how to wring fuels and chemicals out of rock – the word petroleum derives from Latin roots meaning “rock oil”. In the current world, amid concerns that our sources of petroleum are dwindling, we are turning over all stones for suitable alternatives to petroleum. We need to replace an essentially non-renewable resource, petroleum, with renewable fuels and thus make our future sustainable. The major renewable materials on Earth are derived from biological systems that reproduce and replenish themselves. So it is natural to turn to biological systems for producing renewable fuels. This short review focuses on recent advances in engineering organisms and processes to make renewable fuels.

Engineering microbes to produce biofuels. Curr Opin Biotechnol. Nov 9 2010
The current biofuels landscape is chaotic. It is controlled by the rules imposed by economic forces and driven by the necessity of finding new sources of energy, particularly motor fuels. The need is bringing forth great creativity in uncovering new candidate fuel molecules that can be made via metabolic engineering. These next generation fuels include long-chain alcohols, terpenoid hydrocarbons, and diesel-length alkanes. Renewable fuels contain carbon derived from carbon dioxide. The carbon dioxide is derived directly by a photosynthetic fuel-producing organism(s) or via intermediary biomass polymers that were previously derived from carbon dioxide. To use the latter economically, biomass depolymerization processes must improve and this is a very active area of research. There are competitive approaches with some groups using enzyme based methods and others using chemical catalysts. With the former, feedstock and end-product toxicity loom as major problems. Advances chiefly rest on the ability to manipulate biological systems. Computational and modular construction approaches are key. For example, novel metabolic networks have been constructed to make long-chain alcohols and hydrocarbons that have superior fuel properties over ethanol. A particularly exciting approach is to implement a direct utilization of solar energy to make a usable fuel. A number of approaches use the components of current biological systems, but re-engineer them for more direct, efficient production of fuels.

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• Microdiesel: microbiology can reduce your carbon footprint
• New Microbial Fuels

Interfering RNAs (RNAi) are meant to match the sequence of the messenger RNAs made from genes, and then to block or inactivate the mRNA, keeping it from being translated into a harmful protein. One of the main hurdles has been delivering the agents specifically to the cells in which they are needed. An article in this Tuesday’s New York Times drew attention to this problem when reporting that many pharmaceutical companies have suspended their research into RNA interference. But what if you could use a common bacteria to deliver the payload? In work reported in this week’s Proceedings of the National Academies of Sciences, researchers led by Fenyong Liu at UC Berkeley made a modified strain of Salmonella to deliver interfering RNA exactly where it was needed. The result: they inhibited cytomegaloviral infection in mice.

ArsTechnica: Meet the newest virus fighter: Salmonella

See: Oral delivery of RNase P ribozymes by Salmonella inhibits viral infection in mice. PNAS USA February 7, 2011 doi: 10.1073/pnas.1014975108

Avipoxviruses (APVs) are distributed worldwide and cause disease in domestic, pet and wild birds of many species. APVs are transmitted by aerosols and biting insects, particularly mosquitoes and arthropods and are usually named after the bird species from which they were originally isolated. The virus species Fowlpox virus (FWPV) causes disease in poultry and associated mortality is usually low, but in flocks under stress (other diseases, high production) mortality can reach up to 50%. APVs are also major players in viral vaccine vector development for diseases in human and veterinary medicine. Abortive infection in mammalian cells (no production of progeny viruses) and their ability to accommodate multiple gene inserts are some of the characteristics that make APVs promising vaccine vectors. Although abortive infection in mammalian cells conceivably represents a major vaccine bio-safety advantage, molecular mechanisms restricting APVs to certain hosts are not yet fully understood. This review summarizes the current knowledge relating to APVs, including classification, morphogenesis, host-virus interactions, diagnostics and disease, and also highlights the use of APVs as recombinant vaccine vectors.

Avipoxviruses: infection biology and their use as vaccine vectors. Virology Journal 2011, 8:49 doi:10.1186/1743-422X-8-49

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• Lipid Membranes in Poxvirus Replication
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A large fraction of the world’s most widespread and problematic pathogens, such as the influenza virus, seem to persist in nature by evading host immune responses by inducing immunity to genetically and phenotypically plastic epitopes (aka antigenic variation). The more recent re-emergence of pandemic influenza A/H1N1 and avian H5N1 viruses has called attention to the urgent need for more effective influenza vaccines. Developing such vaccines will require more than just moving from an egg-based to a tissue-culture–based manufacturing process. It will also require a new conceptual understanding of pathogen–host interactions, as well as new approaches and technologies to circumvent immune evasion by pathogens capable of more genetic variation. This paper discusses these challenges, focusing on some potentially fruitful directions for future research.

Vaccines often take between 16 and 20 years to develop, and the challenge now is to understand deceptive imprinting better and to systematically identify and characterize deceptive epitopes and low-efficiency, interfering epitopes in influenza and other viruses. Progress would enable targeting of both immunodominant deceptive epitopes and low-efficiency epitopes for genetic modification. In addition, more studies are needed to determine whether such genetic modifications can actually lead to significantly greater vaccine efficacy, but there is great promise in these understanding-driven approaches.

How Can Vaccines Against Influenza and Other Viral Diseases Be Made More Effective? 2010 PLoS Biol 8(12): e1000571. doi:10.1371/journal.pbio.1000571

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• The 2009 H1N1 pandemic – what went right and what went wrong?
• RNA replicons – a new approach to influenza virus vaccines
• Protective immunity against influenza

Recent events have highlighted the damage our dependence on oil can wreak on the natural world. However, as Lena Ciric discusses in this article in Microbiology Today, communities of bacteria have evolved over billions of years to be rather better than we are at breaking down the complex hydrocarbons that are found in oil. How we can exploit this ability to improve our future clean-up strategies?

On 20th April 2010 a massive explosion rang out in the Gulf of Mexico. The source of the incident was the Deepwater Horizon drilling rig, situated about 84 km from the Louisiana coast, which had been drilling for oil at a depth of over 1,500 m. The explosion killed 11 people at the time and was the cause of what is now referred to as the worst environmental disaster in US history. It is difficult to state the exact volume of oil which has spilled into the Gulf of Mexico, the best estimate being put forward by the US government as 4.9 million barrels. That’s over 770 million litres, or over 300 full Olympic-size swimming pools. The well which was the source of the oil spill has since been plugged successfully and a US government report has stated that three-quarters of the spilled oil as now been ‘dealt with’. A considerable proportion of the removal of the spill is attributed to bacterial biodegradation of the hydrocarbons that constitute the crude oil. The huge oil spill in the Gulf of Mexico is only one of a huge number of oil spills that have taken place over the course of Earth’s history. For billions of years, our microbial neighbours have been evolving to utilize the molecules that constitute oil – and it turns out that they have now become quite
good at it.

Read more

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• Molecular approaches to bioremediation

Bacteriophages represent one of the most abundant biological entities in nature and have long been recognized for their potential use as therapeutic agents. In recent years overprescription of antibiotics and the concomitant development of antibiotic-resistant ‘super-bugs’ have highlighted the need for alternative strategies to combat infectious diseases. Consequently, a lot of phage research in the past two decades was aimed at assessing whether phage can be used to eliminate undesirable bacteria. Traceability is a requirement in modern food production, incorporating every step in the production process, commonly known as the ‘farm to fork’ concept (European Commission White paper on Food Safety, January 2000). Phages are omnipresent and are accidentally, yet regularly, consumed through ingestion of water and food. For this reason they are presumed to be safe as undesirable effects have not been reported. This, together with their specificity, makes them excellent tools for food safety purposes.

The ‘farm to fork’ concept identifies quality assurance steps at which bacterial contamination may occur, and which also represent critical points where phage treatments may be applied. The most frequently encountered food pathogens belong to one of the four dominant genera, Salmonella, enterotoxigenic Escherichia coli, Campylobacter and Listeria, along with less common infections by Clostridium spp., Staphylococcus aureus, Streptococcus suis and Cronobacter sakazakii. Phages targeting strains of each of these species have been identified and this review discusses the pros and cons of the use of phages as biocontrol, biosanitation and detection agents.

Bacteriophages as biocontrol agents of food pathogens. Curr Opin Biotechnol. Nov 4 2010
Bacteriophages have long been recognized for their potential as biotherapeutic agents. The recent approval for the use of phages of Listeria monocytogenes for food safety purposes has increased the impetus of phage research to uncover phage-mediated applications with activity against other food pathogens. Areas of emerging and growing significance, such as predictive modelling and genomics, have shown their potential and impact on the development of new technologies to combat food pathogens. This review will highlight recent advances in the research of phages that target food pathogens and that promote their use in biosanitation, while it will also discuss its limitations.

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• Bugs Against Biofilms
• Bacteriophages for plant disease control
• 10 things you should know about E. coli O157

Since the beginning of mankind, human beings have strived to pass on their thoughts and knowledge to other people and to future generations. In this respect, the cultural role played by paper has been immense: paper is used for drawings, books, archival documents, photographs, prints, and so forth. Paper was first made in China around 105 AD, and its history can be roughly divided into two major periods: before the 19th century, when paper was made by hand, cellulose from linen and cotton rags was used as the raw material; from the 19th century onwards, when paper was machine-made from wood pulp, paper has contained several other components in addition to cellulose; these include lignin, hemicellulose and pectin. Furthermore, paper is often coated with sizes (the sizing of paper is a process that renders the sheets impervious to ink) such as gelatine, or with minerals, pigments and other substances to impart desirable properties. Libraries, archives and museums preserve paper material, and such material is at risk of deterioration and needs to be protected from physicochemical and biological agents. In many cases, microbial processes have been implicated in paper deterioration.

Scripta manent? Assessing microbial risk to paper heritage. Trends in Microbiol. Oct 22 2010
Paper, like all other cultural heritage materials, degrades over time, but conservation slows down the rate of its deterioration. There is a long history of cooperation between microbiologists and conservators of libraries and archival materials, but current approaches addressing paper deterioration need urgent reassessment to take full advantage of modern microbiological methodologies. This article discusses what we believe are the current priority research areas in assessing microbial risk to paper heritage, and reports studies on a 13th century Italian manuscript and on Leonardo da Vinci’s Atlantic Codex which illustrate the problems and challenges encountered when dealing with microbial investigations of paper artworks. The potential of using a more advanced microbiological approach is highlighted.

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• The Tomb of the Shroud
• Diseases of dinosaurs
• What have the Romans ever done for us?

Marine natural products are a continued focus for drug discovery and have provided many important therapeutic agents. Lead compounds with biomedical potential have been isolated from marine invertebrates, bacteria, and fungi. Each year numerous compounds with an array of biological activities are reported, but to-date only 13 molecules have entered into the clinical pipeline. Four molecules have been approved for clinical use, one of which is approved only in the EU. The approved molecules include two nucleosides based on sponge-derived nucleosides, a cone snail peptide, and a metabolite isolated from a tunicate. Marine microbes have received growing attention as the sources for bioactive metabolites and have great potential to increase the number of marine natural products in clinical trials. The sustainable and economic supply of the active pharmaceutical ingredient is often easier to achieve for compounds produced through microbial fermentation approaches versus the cultivation of slower growing macroorganisms.

Marine natural products provide an excellent opportunity to study diverse and unique compounds not readily accessible from any other source leading to expansion of the pharmaceutical pipeline. Marine microbes can produce unique compounds covering new chemical space, and the utility of marine natural products is expanding beyond its original role in identification of new prototype drug leads into fields of study involving sustainable supplies of unique molecules using biosynthesis in conjunction with synthesis. Perhaps the greatest impact marine natural products has played is in revealing that unexplored and previously inaccessible chemical space can contribute to growth in the pharmaceutical pipeline. Improved methodologies in fermentation technologies, biosynthesis, and synthesis provide opportunities to both create and supply drug leads that would not be available by any single method independently. As a result pharmaceutical biotechnology in the future is certain to provide increasingly sophisticated molecular architecture assembled using biosynthesis and synthesis in concert.

The expanding role of marine microbes in pharmaceutical development. Curr Opin Biotechnol. Oct 16 2010
Marine microbes have received growing attention as sources of bioactive metabolites and offer a unique opportunity to both increase the number of marine natural products in clinical trials as well as expedite their development. This review focuses specifically on those molecules currently in the clinical pipeline that are established or highly likely to be produced by bacteria based on expanding circumstantial evidence. We also include an example of how compounds from harmful algal blooms may yield both tools for measuring environmental change as well as leads for pharmaceutical development. An example of the karlotoxin class of compounds isolated from the dinoflagellate Karlodinium veneficum reveals a significant environmental impact in the form of massive fish kills, but also provides opportunities to construct new molecules for the control of cancer and serum cholesterol assisted by tools associated with rational drug design.

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