Enzyme inhibitors of microbial origin

The screening for enzyme inhibitors of microbial origin in the past decades has been a prosperous area to find new metabolites that are of potential importance as therapeutic or antibiotic agents. This review attempts a survey of recent achievements in this type of screening. Special emphasis is given to enzyme inhibitors and screening systems in fields where industry has a main interest in development. This includes some notes on the improved methodology for the detection of reversible and irreversible inhibitors of beta-lactamases and the presentation of a unique inhibitor of alpha-amylase from porcine pancreas isolated from a strain of Streptomyces tendae. This inhibitor (HOE 467) may be of potential use in the treatment of diabetic conditions, obesity and adipositas. The results show that the screening for enzyme inhibitors from microorganisms still provides one of the central challenges for future research.     

基于微生物源的抗虫基因发掘

植物转基因抗虫技术在害虫控制方面取得了巨大成功。商业化运用的抗虫基因目前全部来源于苏云金杆菌（Bacillus thuringiensis,Bt）的杀虫晶体蛋白基因,存在抗虫谱较窄及害虫逐渐产生抗性等问题,表明新型抗虫基因的筛选尤为重要。已有的文献研究表明,除了继续发掘Bt来源的新型杀虫蛋白基因以外,非Bt杀虫细菌及杀虫真菌也具有重要的发掘价值。     

Alpha-glucosidase inhibitors of microbial origin]

The data on spreading of inhibitors of alpha-glucosidases with microbial origin are given. Physiochemical characteristics of acorbose--a known inhibitor of alpha-glucosidases--and new inhibitor isolated from Streptomyces sp. are given in detail.     

Low-molecular-weight trypsin inhibitors of microbial origin

Three hundred actinomyces cultures newly isolated from the soil of different regions of the Soviet Union were tested for their ability to produce inhibitors of trypsin-like proteases. Seven previously not known to produce trypsin inhibitors (Streptomyces bikiniensis 17-5, S. sporoclivatus 28-1, S. filamentosus 32-11, S. diastatochromogenes 20-4, S. lavendulae 29-4, S. violacens 52-8, and Streptoverticillium cinnamoneum 36-8) were found to possess high antitrypsin activity. The morphological and cultural properties of the strains and the dynamics of inhibitor production were investigated. S. bikiniensis 17-5 was studied in greatest detail. Its culture filtrate contained several inhibitors for trypsin and one for chymotrypsin. A mixture of oligopeptides with Mr of 300-500 was obtained by the described procedure which included the adsorption of the culture fluid filtrate on charcoal followed by ion-exchange chromatography on CM-cellulose. Four trypsin inhibitors (Sb-IT1, Sb-IT2, Sb-IT3, and Sb-IT4) were isolated from the mixture in a highly purified state by reversed-phase high-performance liquid chromatography. Sb-IT2 has been recognized as formylhistidylvaline with an Mr of 282. No trypsin inhibitor of this structure has been described previously.     

Soil inorganic polyphosphates of microbial origin

Summary Extraction of eight soils with cold 0.5 M perchloric acid yielded acid-labile phosphates in four of them which were shown to be naturally occurring inorganic polyphosphates of microbial origin. The amounts estimated were in the range of 5.0 to 11.1 μg P/g soil. Gel filtration through Sephadex G-25 indicated variation with respect to chain lengths and molecular weights of these polyphosphates. Addition of excess amounts of orthophosphate to 14-day incubated glucose-amended soils resulted in accumulation of larger quantities (up to 22.0 μg P/g soil) of acid-labile polyphosphates in some soils. re]19720407 Department of Agronomy, Ohio State University and Ohio Agricultural Research and Development Center     

Polymethyleneamine alkaloids of animal origin. I. Metabolites of marine and microbial organisms

This review, issued in two parts, describes the information on the structure and biological activity of animal alkaloids derived from polymethyleneamines and produced by marine organisms, wasps, spiders, and microorganisms. Animal alkaloids are outstanding models for developing methods and drugs for the treatment of many human diseases. In the first part, we consider compounds produced by marine and microbial organisms. Some promising synthetic analogues of these alkaloids are used in developing modem preparations for the chelate therapy of excessive blood iron content and antituberculosis, antiproliferative, and immunosuppressive drugs. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.     

Immunomodulating action of peptidoglycan of microbial origin]

The action of a high molecular weight peptidoglycan produced by Agrobacter radiobacter sp. on the functional activity parameters in leukocytes and macrophages i. e. chemotaxis and adhesion was studied. It was shown that the peptidoglycan had a stimulating action on the chemotaxis of cells of the peritoneal exudate. A marked stimulating action of the drug on the primary immune response to the tissue antigen of sheep erythrocytes was observed. The peptidoglycan stimulated the antibody titers and delayed hypersensitivity when administered in various periods after an antigenic stimulus. Multifactorial experiments on the protective action of the peptidoglycan in experimental infections were carried out. Second-order polynomial statistic models characterizing the animal survival rate were constructed and the dose-time parameters of the drug use were optimized.     

Foodborne cryptosporidiosis

Foodborne illness, the majority of which is caused by enteric infectious agents, costs global economies billions of dollars each year. The protozoan parasite Cryptosporidium is particularly suited to foodborne transmission and is responsible for >8?million cases of foodborne illness annually. Procedures have been developed for sensitive detection of Cryptosporidium oocysts on fresh produce and molecular diagnostic assays have been widely used in case linkages and infection source tracking, especially during outbreak investigations. The integrated use of advanced diagnostic techniques with conventional epidemiological studies is essential to improve our understanding of the occurrence, source and epidemiology of foodborne cryptosporidiosis. The implementation of food safety management tools such as Good Hygienic Practices (GHP), Hazard Analysis and Critical Control Points (HACCP), and Quantitative Microbial Risk Assessment (QMRA) in industrialised nations and Water, Sanitation, and Hygiene (WASH) in developing countries is central for prevention and control and foodborne cryptosporidiosis in the future.     

Foodborne viruses

Foodborne and waterborne viral infections are increasingly recognized as causes of illness in humans. This increase is partly explained by changes in food processing and consumption patterns that lead to the worldwide availability of high-risk food. As a result, vast outbreaks may occur due to contamination of food by a single foodhandler or at a single source. Although there are numerous fecal-orally transmitted viruses, most reports of foodborne transmission describe infections with Norwalk-like caliciviruses (NLV) and hepatitis A virus (HAV), suggesting that these viruses are associated with the greatest risk of foodborne transmission. NLV and HAV can be transmitted from person to person, or indirectly via food, water, or fomites contaminated with virus-containing feces or vomit. People can be infected without showing symptoms. The high frequency of secondary cases of NLV illness and - to a lesser extent - of hepatitis A following a foodborne outbreak results in amplification of the problem. The burden of illness is highest in the elderly, and therefore is likely to increase due to the aging population. For HAV, the burden of illness may increase following hygienic control measures, due to a decreasing population of naturally immune individuals and a concurrent increase in the population at risk. Recent advances in the research of NLV and HAV have led to the development of molecular methods which can be used for molecular tracing of virus strains. These methods can be and have been used for the detection of common source outbreaks. While traditionally certain foods have been implicated in virus outbreaks, it is clear that almost any food item can be involved, provided it has been handled by an infected person. There are no established methods for detection of viruses in foods other than shellfish. Little information is available on disinfection and preventive measures specifically for these viruses. Studies addressing this issue are hampered by the lack of culture systems. As currently available routine monitoring systems exclusively focus on bacterial pathogens, efforts should be made to combine epidemiological and virological information for a combined laboratory-based rapid detection system for foodborne viruses. With better surveillance, including typing information, outbreaks of foodborne infections could be reported faster to prevent further spread.