Arsenic is the most common toxic substance in the environment, ranking first on the US Superfund list of hazardous substances. It is introduced to the environment primarily from geologic sources and is acted on biologically, creating an arsenic biogeocycle. Geothermal environments are well known for their elevated arsenic content and thus provide an excellent setting in which to study microbe–arsenic interactions. So far, studies aimed at identifying the organisms participating in these and other arsenic transformations have focused almost entirely on microorganisms belonging to the domains Archaea and Bacteria. In contrast, comparatively little attention has been paid to the Eukarya that inhabit these extreme environments, much less their potential contribution to biogeochemical cycles in these extreme habitats. Now it would appear that algae play a significant role in arsenic cycling in the geothermal environment as also found in a range of marine and freshwater environments. These observations indicate that arsenic methylation forms an important component of the global arsenic biogeocycle.
Biotransformation of arsenic by a Yellowstone thermoacidophilic eukaryotic alga. PNAS USA March 10, 2009
Arsenic is the most common toxic substance in the environment, ranking first on the Superfund list of hazardous substances. It is introduced primarily from geochemical sources and is acted on biologically, creating an arsenic biogeocycle. Geothermal environments are known for their elevated arsenic content and thus provide an excellent setting in which to study microbial redox transformations of arsenic. To date, most studies of microbial communities in geothermal environments have focused on Bacteria and Archaea, with little attention to eukaryotic microorganisms. Here, we show the potential of an extremophilic eukaryotic alga of the order Cyanidiales to influence arsenic cycling at elevated temperatures. Cyanidioschyzon sp. isolate 5508 oxidized arsenite [As(III)] to arsenate [As(V)], reduced As(V) to As(III), and methylated As(III) to form trimethylarsine oxide (TMAO) and dimethylarsenate [DMAs(V)]. Two arsenic methyltransferase genes, CmarsM7 and CmarsM8, were cloned from this organism and demonstrated to confer resistance to As(III) in an arsenite hypersensitive strain of Escherichia coli. The two recombinant CmArsMs were purified and shown to transform As(III) into monomethylarsenite, DMAs(V), TMAO, and trimethylarsine gas, with a Topt of 60–70°C. These studies illustrate the importance of eukaryotic microorganisms to the biogeochemical cycling of arsenic in geothermal systems, offer a molecular explanation for how these algae tolerate arsenic in their environment, and provide the characterization of algal methyltransferases.
There are many options still available for new antibiotics. While the search for new drugs seems to be declining, in this article in Microbiology Today, Flavia Marinelli takes a look at the need for new antimicrobials:
Novel classes of antibiotics are constantly required due to the expanding population of patients at risk and the growing prevalence of resistant pathogens in hospital- or community-acquired infections. Despite this need, major pharmaceutical players seem to be reducing their efforts to discover new antibiotics. This is due to a combination of factors such as the maturity, great competition and increased genericization of the antibiotic market. Unrealized expectations from high-throughput screening, combinatorial chemistry and pathogen-genome-derived targets have also had a negative effect. The perception prevails that the discovery of novel antibiotics is a very rare event. On the other hand, past and present successes speak for a return to microbial product screening.
Measles virus (MV) is one of the most contagious human pathogens. It is transmitted by aerosols, infecting a new host via the upper respiratory tract. Eventually, infection can spread to many organs of the body. The host cell receptors for MV are well defined: CD46, a member of the human complement regulatory proteins and a ubiquitous cellular receptor found on all nucleated cells, and CD150 or SLAM (signalling lymphocyte activation molecule), a membrane glycoprotein present on activated B cells, T cells and monocytes. It is generally believed that laboratory and vaccine strains of MV use both CD150 and CD46 as their cellular receptors, but wild-type MV strains mainly use CD150.
Oncolytic viruses have been selected or engineered to replicate in tumour cells. Approaches towards targeting cancer cells frequently exploit antigens that are unique to or are over expressed on the surface of tumour cells. As cell surface recognition and virus entry is the key first step for specific targeting, engineering oncolytic viruses in order to recognize exclusively the tumour cell-surface is important. Therefore, retargeting of oncolytic viruses a promising approach to exploit the potential of virotherapy.
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Although virotherapy of hard-to-treat tumours with engineered viruses is a tantalizing prospect, this approach is still limited to laboratory studies at present. In order to develop a practical oncolytic treatments, successful tests in vitro using susceptible cells must lead to evaluation of the efficacy of tumour reduction in vivo in animal models with objective measurable parameters of safety and efficacy. Only then will we be ready to begin consideration of human trials of these potent new weapons in the fight against cancer.
GlaxoSmithKline, the world’s second biggest pharmaceutical company, is to provide cheap drugs to millions of people in the developing world. Andrew Witty, the new head of the company, has said he will cut prices on all medicines, including HIV treatments, in the 50 poorest countries to no more than 25 per cent of the levels in Britain and the US. The company will also give back 20 per cent of profits to be spent on hospitals and clinics and share knowledge about potential drugs currently protected by patents. Drug companies have been repeatedly criticised for failing to drop prices for HIV drugs as millions have died in Africa and Asia.
Dr. Peter Palese describes how reconstructing the extinct 1918 pandemic influenza virus by reverse genetics can help us better understand molecular basis of virulence and the mechanisms by which pandemic influenza viruses are transmitted.
MicroRNAs (miRNAs) are a class of small (~21–25 nucleotides) single-stranded RNAs that can inhibit the expression of specific messenger RNAs by binding to complementary target sequences within the mRNAs. Given the propensity of viruses to co-opt cellular pathways and activities for their benefit, it is perhaps not surprising that several viruses have now been shown to reshape the cellular environment by reprogramming the host’s RNA-interference machinery. In particular, microRNAs are produced by the various members of the herpesvirus family during both the latent stage of the viral life cycle and the lytic (or productive) stage. Emerging data suggest that viral microRNAs are particularly important for regulating the transition from latent to lytic replication and for attenuating antiviral immune responses.
At present, there is no evidence that any vertebrate virus encodes novel miRNA-processing factors or RISC components. So it seems that, in general, viral miRNAs are transcribed and processed in the same way as cellular miRNAs. Despite our still limited knowledge of viral miRNA functions, the large number of miRNAs that are encoded by diverse members of the herpesvirus family, and their high-level expression during latent infections, suggests that these small non-coding RNAs have a key role in regulating viral pathogenesis in vivo. In particular, it will be important to test the hypothesis that herpesvirus miRNAs that are produced during latency help to maintain the latent state, which could be examined by using viral mutants and/or antisense reagents. It certainly seems possible that antisense reagents specific for particular viral miRNAs could significantly attenuate herpesvirus-induced diseases in humans, if they could be delivered effectively to infected cells in vivo – like this!
What is genomics? How will it affect our lives? In this primer on the genomics revolution, entrepreneur Barry Schuler says we can at least expect healthier, tastier food. He suggests we start with the pinot noir grape, to build better wines.
MicrobiologyBytes has discussed before Craig Venter’s attempts to create a synthetic microorganism. In 2008, Venter described his work at the TED Conference, and his talk is well worth watching:
Bioremediation can be defined as a process that uses microorganisms, fungi, green plants or their enzymes to return the natural environment altered by contaminants to its original condition. A major advantage of bioremediation is its reduced cost compared to conventional cleanup techniques – the cost of remediation for all contaminated sites in the USA alone is estimated to be $1.7 trillion (Molecular approaches in bioremediation. Curr Opin Biotechnol. Nov 12 2008). In addition, bioremediation is often a permanent solution providing complete transformation of the pollutant to its molecular constituents like carbon dioxide and water rather than a partial method that transfers wastes from one phase to another. Unfortunately, there are many man-made compounds that lack good biological catalysts, and many instances where good biocatalysts fail to transform pollutants in the environment.
Bacteria have enormous potential for cleaning up wastes; however, the interactions between bacteria and pollutants are complex and suitable outcomes do not always take place. Hence, molecular approaches are being applied to enhance bioremediation. One advance in bioremediation to improve the stability of the biocatalyst is to create a system where degradation occurs in the area near the roots of plants known as the rhizosphere. In rhizoremediation, the bacteria degrade the pollutants while the plant roots provide a niche for the microorganism and key nutrients. The advantages of rhizoremediation include the ability of plant roots to provide a large surface area for bacterial propagation and biofilm formation, the roots transport the bacteria through the contaminated soil, the roots provide a niche for the bacteria by providing nutrients, and the roots facilitate oxygen exchange. Successful rhizoremediation systems have been established for pollutants such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls (PCBs), fuels, metals, and pesticides such as parathion.
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Directed evolution or DNA shuffling is a powerful mutagenesis technique that mimics the natural molecular evolution of genes in order to efficiently re-design them. Its power lies in the fact that it can introduce multiple mutations into a gene in order to create new enzymatic activity, which can be discovered by a suitable method of selection (bioassays). Family shuffling applies DNA shuffling to groups of related genes to combine them in a manner that accelerates directed evolution. Genome shuffling recombines the chromosomes of several bacteria to enhance the activity of the whole organism.
Metabolic engineering involves redirecting a cell’s metabolism to achieve a particular goal using recombinant engineering. This technique has been used to create bacterial strains that degrade chlorinated ethenes through the addition of several cloned enzymes to the cell. Metabolic engineering has also been used successfully to handle difficult mixtures of pollutants.
Whole-transcriptome profiling using DNA microarrays has the advantage that the relative amount of transcripts from the whole genome may be easily determined compared to such techniques like proteomics. To understand the metabolism of bacteria in the rhizosphere, researchers have begun to utilize whole-genome profiling.
Although a tremendous amount of work remains to be performed, significant advances have been made through protein engineering and through metabolic engineering for the purposes of bioremediation. However, even though whole-transcriptome profiling and proteomics are utilized routinely in some disciplines, they remain to be utilized extensively in bioremediation. Furthermore, it is important to ensure engineered strains for field use are competitive; rhizoremediation can provide a niche for these engineered bacteria. Chromosomal integration of introduced genes can limit horizontal gene transfer to other species, but this should also be empirically verified to ensure that no adverse environmental effects occur.
Arsenic is the most common toxic substance in the environment, ranking first on the US Superfund list of hazardous substances. It is introduced to the environment primarily from geologic sources and is acted on biologically, creating an arsenic biogeocycle. Geothermal environments are well known for their elevated arsenic content and thus provide an excellent setting in which to study microbe–arsenic interactions. So far, studies aimed at identifying the organisms participating in these and other arsenic transformations have focused almost entirely on microorganisms belonging to the domains Archaea and Bacteria. In contrast, comparatively little attention has been paid to the Eukarya that inhabit these extreme environments, much less their potential contribution to biogeochemical cycles in these extreme habitats. Now it would appear that algae play a significant role in arsenic cycling in the geothermal environment as also found in a range of marine and freshwater environments. These observations indicate that arsenic methylation forms an important component of the global arsenic biogeocycle.
