Nation unprepared for microbial threats, IOM reports.
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Anti-Infective Agents↗
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Recent developments in enzyme and microbial biotechnology--strategies in bioprocess design.
Microorganisms have been used traditionally by industry as sources of natural products, or as sources of enzymes capable of mediating specific chemical transformations. This situation has changed radically in recent years, a time during which we have seen a dramatic increase in the number and range of potential biotechnological applications of enzymes and their genetically-engineered variants. An increasing number of enzymes, receptors and other proteins have now been structurally characterized, and their genes isolated as a basis for producing recombinant proteins for genetic analysis of their structure and function. These innovations have necessitated development of associated technologies for large-scale production of proteins in bioreactors, appropriate strategies for quality control, and new analytical tools for structural characterization of recombinant gene products. Some recombinant proteins are already in an advanced stage of development for use either as new-generation therapeutics, as target molecules for "intelligent" drug screening, or as biological components of biosensors. As the predictive power of protein model building improves, the diversity of applications of such technology will increase further as it becomes feasible to generate totally synthetic proteins with specifically-tailored properties.
Biosensing Techniques↗
Integrating metabolomics into a systems biology framework to exploit metabolic complexity: strategies and applications in microorganisms.
As an important functional genomic tool, metabolomics has been illustrated in detail in recent years, especially in plant science. However, the microbial category also has the potential to benefit from integration of metabolomics into system frameworks. In this article, we first examine the concepts and brief history of metabolomics. Next, we summarize metabolomic research processes and analytical platforms in strain improvements. The application cases of metabolomics in microorganisms answer what the metabolomics can do in strain improvements. The position of metabolomics in this systems biology framework and the real cases of integrating metabolomics into a system framework to explore the microbial metabolic complexity are also illustrated in this paper.
Bacteria↗
Antimicrobial and hemolytic activities of crabrolin, a 13-residue peptide from the venom of the European hornet, Vespa crabro, and its analogs.
The venom of insects like bee, hornet and wasp contain peptides that exhibit potent biological activities. Many of these peptides are composed of 13-26 residues and are thus accessible through chemical synthesis as well as amenable to studies directed toward structure-function correlations. In this report, we describe antibacterial and hemolytic activities of crabrolin: FLPLILRKIVTAL-NH2, a 13-residue-peptide present in the venom of the hornet Vespa crabro and related peptides. The analogs were chosen so that the role of proline and positively charged amino acids in modulating biological activities could be evaluated. Our results indicate that, although helical conformation is necessary for hemolytic activity, it is not a prerequisite for antibacterial activity. Appropriately positioned, charged and hydrophobic residues and overall hydrophobicity appear to determine antibacterial activity. The discovery of a large number of host-defense peptides in a variety of species in recent years offers a large repertoire of molecules that can be "engineered" based on biophysical principles to yield molecules with specific activities.
Animals↗
'Molecular farming' of antibodies in plants.
'Molecular farming' is the production of valuable recombinant proteins in transgenic organisms on an agricultural scale. While plants have long been used as a source of medicinal compounds, molecular farming represents a novel source of molecular medicines, such as plasma proteins, enzymes, growth factors, vaccines and recombinant antibodies, whose medical benefits are understood at a molecular level. Until recently, the broad use of molecular medicines was limited because of the difficulty in producing these proteins outside animals or animal cell culture. The application of molecular biology and plant biotechnology in the 1990s showed that many molecular medicines or vaccines could be synthesised in plants and this technology is termed 'molecular farming'. It results in pharmaceuticals that are safer, easier to produce and less expensive than those produced in animals or microbial culture. An advantage of molecular farming lies in the ability to perform protein production on a massive scale using hectares of cultivated plants. These plants can then be harvested and transported using the agricultural infrastructure. Thus, molecular farming allows rapid progress from genetic engineering to crop production, and new cash crops producing recombinant proteins are already being commercially exploited. We speculate that as functional genomics teaches us more about the nature of disease, molecular farming will produce many of the protein therapeutics that can remedy it.
Animals↗
Evaluation of the effectiveness of the Pastormaster method for disinfection of legionella in a hospital water distribution system.
The Pastormaster method consists of heating the water of hospital distribution systems at a specific point to a sufficient temperature for a minimum amount of time to eradicate legionella. The object of this study was to evaluate the effectiveness of the Pastormaster method for legionella disinfection in a hospital environment. A two-phase procedure was performed: hydraulic optimization of the water supply circuit, and implementation of the Pastormaster method. Water samples were taken at 10 representative points in the hospital hot-water system and cultured microbiologically. Other physical and chemical measurements were also determined. Implementation of the Pastormaster method and correction of the deficiencies identified during a hydraulic system audit confirmed the absence of legionella in the hospital water distribution system. The combination of implementation of the Pastormaster method and conduction of a hydraulic audit designed to identify and remedy any possible problems in water circulation is effective in minimizing the risk of legionella contamination in hospital water distribution systems.
Colony Count, Microbial↗
Bioavailability and biotransformation of the mutagenic component of particulate emissions present in motor exhaust samples.
The pharmacokinetic concepts of bioavailability and biotransformation are introduced into the assessment of public health risk from experimental data concerning the emissions of potentially mutagenic and carcinogenic substances from motor vehicles. The inappropriateness of an automatic application in the risk assessment process of analytical or experimental results, obtained with extracts and procedures incompatible with the biological environment, is illustrated on the discrepancy between short-term laboratory tests predictions that wider use of diesel engines on our roads will increase the risk of respiratory cancer and the widely negative epidemiological evidence. Mutagenic activity of diesel particulates was minimal or negative when tested in extracts obtained with biological fluids, was substantially dependent on the presence of nitroreductase in the microbial tester strain, and disappeared completely 48 hr after the diesel particles had been phagocytized by alveolar macrophages. Similarly, long-term animal inhalation exposures to high concentrations of diesel particles did not induce the activity of hydrocarbon metabolizing enzymes or specific adverse immune response unless organic solvent extracts of diesel particles were administered intratracheally or parenterally in doses that highly exceed the predicted levels of public exposure even by the year 2000. Furthermore, the suspected cancer producing effects of inhaled diesel particles have thus far not been verified by experimental animal models or available long-term epidemiological observations. It is concluded that unless the biological accessibility of the active component on the pollutant as well as its biotransformation and clearance by natural defense mechanisms are considered, lung cancer risk assessment based solely on laboratory microbial tests will remain an arbitrary and unrealistic process and will not provide meaningful information on the potential health hazard of a pollutant.
Air Pollutants↗
Communicable disease control and public policy in the 1970s--hot war, cold war, or peaceful coexistence?
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Animals↗
Trichosporon asahii fungemia in a patient with non-hematological malignancy.
Trichosporon fungemia is usually seen in neutropenic patients with underlying hematological malignancies. In this report we describe a fatal case of Trichosporon asahii fungemia in a non-neutropenic patient with a non-hematological malignancy. For 1 week the patient exhibited hematuria, weakness, easy fatigability and headaches. At admission she had anemia, renal failure and evidence of right hydronephrosis and bladder wall masses as detected by CT scan. She did not have a history of tobacco abuse, contact with urinary carcinogens or Schistosoma infestation; her clinical picture was suggestive of bladder cancer. After some investigations the patient underwent radical cystectomy and ileal conduit surgery because of transitional cell carcinoma in the urinary bladder. After an initial uneventful improvement postoperatively the patient deteriorated and died of septic shock despite all reanimation efforts and antibiotherapy including fluconazole. The blood culture obtained 4 days before the patient died revealed T. asahii, which was isolated on the day she died and found to be resistant to fluconazole and caspofungin. This report suggests that clinicians remain aware that T. asahii fungemia may develop in clinically deteriorated patients even if they do not have a hematological malignancy.
Aged↗
Genetic engineering of Escherichia coli for production of tetrahydrobiopterin.
Tetrahydrobiopterin (BH4) is an essential cofactor for various enzymes in mammals. In vivo, it is synthesized from GTP via the three-step pathway of GTP cyclohydrolase I (GCHI), 6-pyruvoyl-tetrahydropterin synthase (PTPS) and sepiapterin reductase (SPR). BH4 is a medicine used to treat atypical hyperphenylalaninemia. It is currently synthesized by chemical means, which consists of many steps, and requires costly materials and complicated procedures. To explore an alternative microbial method for BH4 production, we utilized recombinant DNA technology to construct recombinant Escherichia coli (E. coli) strains carrying genes expressing GCHI, PTPS and SPR enzymes. These strains successfully produced BH4, which was detected as dihydrobiopterin and biopterin, oxidation products of BH4. In order to increase BH4 productivity we made further improvements. First, to increase the de novo GTP supply, an 8-azaguanine resistant mutant was isolated and an additional guaBA operon was introduced. Second, to augment the activity of GCHI, the folE gene from E. coli was replaced by the mtrA gene from Bacillus subtilis. These modifications provided us with a strain showing significantly higher productivity, up to 4.0 g of biopterin/L of culture broth. The results suggest the possibility of commercial BH4 production by our method.
Alcohol Oxidoreductases↗
Regenerative dental medicine: stem cells and tissue engineering in dentistry.
The dawn of this century is brightened by the growing understanding and experimentation with stem cells as primary tools in the expanding regenerative medicine and tissue engineering revolution. The tradition of using prosthetic artificial implants to restore lost or damaged dental tissue will gradually be supplanted by more natural alternatives, including biological tooth replacement or induction. The practice of dentistry is likely to be revolutionized by biological therapies based on growth and differentiation factors that accelerate and/or induce a natural biological regeneration. This prospect has flourished from the gained knowledge provided by the molecular biological characterization of the genetic makeup of human cells and from a growing understanding of the effect of environmental factors. Prevention of dental diseases will also gain new ground as more insight is gained into the genetic makeup of microbial pathogens, their interactions with the host, and the host repair mechanisms. This review summarizes current knowledge, barriers, and challenges in the clinical use of stem cells with an emphasis on applications in dentistry.
Animals↗
Resource and energy recovery options for fermentation industry residuals.
Over the last 40 years, the fermentation industry has provided facility planners, plant operators and environmental engineers with a wide range of residuals management challenges and resource/energy recovery opportunities. In response, the industry has helped pioneer the use of a number of innovative resource and energy recovery technologies. Production of animal feed supplements, composts, fertilizers, soil amendments, commercial baking additives and microbial protein materials have all been detailed in the literature. In many such cases, recovery of by-products significantly reduces the need for treatment and disposal facilities. Stable, reliable anaerobic biological treatment processes have also been developed to recovery significant amounts of energy in the form of methane gas. Alternatively, dewatered or condensed organic fermentation industry residuals have been used as fuels for incineration-based energy recovery systems. The sale or use of recovered by-products and/or energy can be used to offset required processing costs and provide a technically and environmentally viable alternative to traditional treatment and disposal strategies. This review examines resource recovery options currently used or proposed for fermentation industry residuals and the conditions necessary for their successful application.
Journal Article↗
Modelling inactivation of Staphylococcus aureus and Yersinia enterocolitica by high-pressure homogenisation at different temperatures.
A detailed study of the inactivation of Staphylococcus aureus and Yersinia enterocolitica by high-pressure homogenisation was performed at, respectively, 25 and 35 different combinations of process temperature and process pressure covering a range of 5-50 degrees C and 100-300 MPa. It appeared that in the entire studied pressure-temperature domain, S. aureus was more resistant to high-pressure homogenisation than Y. enterocolitica. Furthermore, the effect of the process pressure on the inactivation of S. aureus was considerably smaller than on the inactivation of Y. enterocolitica. Also, temperature between 5 and 40 degrees C did not affect inactivation of S. aureus by high-pressure homogenisation, while Y. enterocolitica inactivation was affected by temperature over a much wider range. Different mathematical models were compared to describe the inactivation of both bacteria under the experimental conditions applied. Such pressure-temperature inactivation models form the engineering basis for design, evaluation and optimisation of high-pressure homogenisation processes as a new preservation technique.
Colony Count, Microbial↗
The role of cell immobilization in fermentation technology.
The distinction between immobilized cell fermentation and immobilized cell biocatalysis is seldom made, though they are conceptually quite different. Unlike immobilized enzyme systems, immobilized viable cells can be used to carry out conventional fermentations. Microbial cells which would otherwise be freely dispersed (in almost colloidal suspension) within the fermentation environment can be encouraged to become attached in some way to a support (carrier), thus producing a discrete particulate solid phase. Such immobilization offers several potential advantages of a process engineering nature to the fermentation system. These include ease of handling and of cell separation, and lowering of bulk viscosity, as well as the obvious potential benefits of increased cell concentration.
Biotechnology↗
Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases.
Several major diseases of old age, including atherosclerosis, macular degeneration and neurodegenerative diseases are associated with the intracellular accumulation of substances that impair cellular function and viability. Moreover, the accumulation of lipofuscin, a substance that may have similarly deleterious effects, is one of the most universal markers of aging in postmitotic cells. Reversing this accumulation may thus be valuable, but has proven challenging, doubtless because substances resistant to cellular catabolism are inherently hard to degrade. We suggest a radically new approach: augmenting humans' natural catabolic machinery with microbial enzymes. Many recalcitrant organic molecules are naturally degraded in the soil. Since the soil in certain environments - graveyards, for example - is enriched in human remains but does not accumulate these substances, it presumably harbours microbes that degrade them. The enzymes responsible could be identified and engineered to metabolise these substances in vivo. Here, we survey a range of such substances, their putative roles in age-related diseases and the possible benefits of their removal. We discuss how microbes capable of degrading them can be isolated, characterised and their relevant enzymes engineered for this purpose and ways to avoid potential side-effects.
Aging↗
Antimicrobial peptides in mucosal secretions: the importance of local secretions in mitigating infection.
The antimicrobial activity of the collective molecules comprising human milk reflects an evolutionarily successful paradigm for preventing and limiting microbial infection. Understanding the molecules that participate in this process and how they work can yield insight into potentially new antimicrobial therapies. Upon proteolytic processing, antimicrobial peptides can be derived from milk proteins, such as lactoferrin, casein, and lysozyme. Similarly, using the HIV-1 gp41 protein template, we have demonstrated that the 28-residue C-terminus, when produced as an independent peptide, exhibits selective toxicity for bacteria over eukaryotic cells. Upon optimizing this sequence for cationic charge and hydrophobic character presented as a alpha-helical structure, we show improved capability of the parent LLP1 sequence to selectively kill bacteria in the host environment and that this activity is increased by the inclusion of Trp residues on the hydrophobic face. We report that it is possible to (i) design de novo antimicrobial peptides that demonstrate optimal antimicrobial activity with minimal inflammatory activity and (ii) design antimicrobial peptides to function in a defined environment. In the end, we describe a de novo designed antimicrobial peptide, WLBU2, which is selectively toxic to microbial pathogens in complex environments and does not stimulate a significant immunomodulatory response. In spite of these properties, WLBU2 activity against Pseudomonas aeruginosa in human milk is inferior to the host peptide LL37 with regard to antimicrobial potency. These studies demonstrate that antimicrobial peptides can be engineered for greater potency in one medium but may not be optimal for working in a different medium such as human milk.
Amino Acid Sequence↗
Geophysical monitoring of a field-scale biostimulation pilot project.
The USGS conducted a geophysical investigation in support of a U.S. Naval Facilities Engineering Command, Southern Division field-scale biostimulation pilot project at Anoka County Riverfront Park (ACP), down-gradient of the Naval Industrial Reserve Ordnance Plant, Fridley, Minnesota. The goal of the pilot project is to evaluate subsurface injection of vegetable oil emulsion (VOE) to stimulate microbial degradation of chlorinated hydrocarbons. To monitor the emplacement and movement of the VOE and changes in water chemistry resulting from VOE dissolution and/or enhanced biological activity, the USGS acquired cross-hole radar zero-offset profiles, travel-time tomograms, and borehole geophysical logs during five site visits over 1.5 years. Analysis of pre- and postinjection data sets using petrophysical models developed to estimate VOE saturation and changes in total dissolved solids provides insights into the spatial and temporal distribution of VOE and ground water with altered chemistry. Radar slowness-difference tomograms and zero-offset slowness profiles indicate that the VOE remained close to the injection wells, whereas radar attenuation profiles and electromagnetic induction logs indicate that bulk electrical conductivity increased down-gradient of the injection zone, diagnostic of changing water chemistry. Geophysical logs indicate that some screened intervals were located above or below zones of elevated dissolved solids; hence, the geophysical data provide a broader context for interpretation of water samples and evaluation of the biostimulation effort. Our results include (1) demonstration of field and data analysis methods for geophysical monitoring of VOE biostimulation and (2) site-specific insights into the spatial and temporal distributions of VOE at the ACP.
Environmental Monitoring↗
New perspectives on microbial dehalogenation of chlorinated solvents: insights from the field.
A variety of microbial dechlorination mechanisms have been demonstrated in laboratory microcosms, pure cultures, and in situ sedimentary environments. New perspectives on in situ processes from these efforts allow the design of more realistic bioremediation strategies that complement natural processes regardless of whether the strategy used is one of engineered accelerated bioremediation or natural attenuation. Since 1994 the scientific community has acquired considerable knowledge regarding natural attenuation of organochlorine compounds. Natural attenuation of chlorinated solvents has been documented at a number of field sites. Reductive dechlorination driven by co-contaminants or naturally occurring organics as substrates in combination with aerobic or co-metabolic degradation contains certain chlorinated solvent plumes. Although natural attenuation is not a panacea, at sites where it is applicable, it offers a scientifically sound, cost-effective method to remediate groundwater contaminated with chlorinated solvents.
Anaerobiosis↗