Showing papers by "Arnold L. Demain published in 2010"

Recombinant organisms for production of industrial products

Abstract: A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding techniques and their modifications are contributing greatly to the development of improved industrial processes. In addition, functional genomics, proteomics and metabolomics are being exploited for the discovery of novel valuable small molecules for medicine as well as enzymes for catalysis. The sequencing of industrial microbal genomes is being carried out which bodes well for future process improvement and discovery of new industrial products.

Avoidance of suicide in antibiotic-producing microbes

Abstract: Many microbes synthesize potentially autotoxic antibiotics, mainly as secondary metabolites, against which they need to protect themselves. This is done in various ways, ranging from target-based strategies (i.e. modification of normal drug receptors or de novo synthesis of the latter in drug-resistant form) to the adoption of metabolic shielding and/or efflux strategies that prevent drug–target interactions. These self-defence mechanisms have been studied most intensively in antibiotic-producing prokaryotes, of which the most prolific are the actinomycetes. Only a few documented examples pertain to lower eukaryotes while higher organisms have hardly been addressed in this context. Thus, many plant alkaloids, variously described as herbivore repellents or nitrogen excretion devices, are truly antibiotics—even if toxic to humans. As just one example, bulbs of Narcissus spp. (including the King Alfred daffodil) accumulate narciclasine that binds to the larger subunit of the eukaryotic ribosome and inhibits peptide bond formation. However, ribosomes in the Amaryllidaceae have not been tested for possible resistance to narciclasine and other alkaloids. Clearly, the prevalence of suicide avoidance is likely to extend well beyond the remit of the present article.

Do we need new antibiotics? The search for new targets and new compounds.

Abstract: Resistance to antibiotics and other antimicrobial compounds continues to increase. There are several possibilities for protection against pathogenic microorganisms, for instance, preparation of new vaccines against resistant bacterial strains, use of specific bacteriophages, and searching for new antibiotics. The antibiotic search includes: (1) looking for new antibiotics from nontraditional or less traditional sources, (2) sequencing microbial genomes with the aim of finding genes specifying biosynthesis of antibiotics, (3) analyzing DNA from the environment (metagenomics), (4) reexamining forgotten natural compounds and products of their transformations, and (5) investigating new antibiotic targets in pathogenic bacteria.

Manual of industrial microbiology and biotechnology.

Abstract: MANUAL OF INDUSTRIAL MICROBIOLOGY AND BIOTECHNOLOGY , MANUAL OF INDUSTRIAL MICROBIOLOGY AND BIOTECHNOLOGY , کتابخانه مرکزی دانشگاه علوم پزشکی ایران

Antibiotics: Natural Products Essential to Human Health

Abstract: For more than 50 years, natural products have served us well in combating infectious bacteria and fungi. Microbial and plant secondary metabolites helped to double our life span during the 20th century, reduced pain and suffering, and revolutionized medicine. Most antibiotics are either (i) natural products of microorganisms, (ii) semi-synthetically produced from natural products, or (iii) chemically synthesized based on the structure of the natural products. Production of antibiotics began with penicillin in the late 1940s and proceeded with great success until the 1970-1980s when it became harder and harder to discover new and useful products. Furthermore, resistance development in pathogens became a major problem, which is still with us today. In addition, new pathogens are continually emerging and there are still bacteria that are not eliminated by any antibiotic, e.g., Pseudomonas aeruginosa. In addition to these problems, many of the major pharmaceutical companies have abandoned the antibiotic field, leaving much of the discovery efforts to small companies, new companies, and the biotechnology industries. Despite these problems, development of new antibiotics has continued, albeit at a much lower pace than in the last century. We have seen the (i) appearance of newly discovered antibiotics (e.g., candins), (ii) development of old but unutilized antibiotics (e.g., daptomycin), (iii) production of new semi-synthetic versions of old antibiotics (e.g., glycylcyclines, streptogrammins), as well as the (iv) very useful application of old but underutilized antibiotics (e.g., teicoplanin).

Antimicrobial spectrum of the antitumor agent, cisplatin.

Abstract: Cisplatin (cisplatinum, cis-diamminedichloroplatinum [II]), is one of the most important anticancer agents used in medicine. Its structure is shown in Figure 1. Owing to its ability to bind to DNA, cause the cross-linking of adjacent intrastrand purines, and interfere with DNA repair, cisplatin is an effective DNA-damaging and anticancer agent. Although cisplatin is nearly curative for testicular cancer and active against ovarian, head and neck cancer, the potential of this drug as a cure for many other types of cancer is limited because of cellular resistance to cisplatin1 and cisplatin’s toxicity to humans; for example, renal toxicity, emesis, neurotoxicity, bone marrow suppression, anemia and hearing loss. Owing to the toxicity, cisplatin is administered intravenously in low dosage. The inhibition of Escherichia coli by cisplatin was discovered by Rosenberg et al.2–4 before it was known to be an effective antitumor agent. They made this discovery while performing an experiment to analyze the effect of an electric field on the growth of bacteria, the experiment involving the use of platinum electrodes. Although Rosenberg et al.3 found that E. coli and other Gramnegative bacteria such as Aerobacter aerogenes, Alcaligenes faecalis, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae and Serratia marcescens were sensitive to cisplatin, it was unclear whether other bacteria were also inhibited. At a concentration 15-fold higher than that which inhibited cell elongation in E. coli, Gram-positive bacteria such as Streptococcus lactis, Streptococcus faecalis, Staphylococcus aureus, Sarcina lutea and Neisseria catarrhalis were not inhibited. Although other Gram-positive organisms were inhibited by this high concentration of cisplatin, they were much more resistant than E. coli. We felt it important to revisit this situation and determine the antimicrobial spectrum of cisplatin. Since those early days, three yeasts have been reported to be inhibited by cisplatin; that is, Saccharomyces cerevisiae,5 Schizosaccharomyces pombe6 and Candida albicans.7 One mold, Dictyostelium discoideum, has been reported to be sensitive to cisplatin.8 However, there has been very little screening effort focusing on the molds. Hence, we felt it important to expand our screening effort to include more filamentous fungi. Inhibition of Gram-negative bacteria E. coli, A. aerogenes, A. faecalis, P. mirabilis, P. aeruginosa, K. pneumoniae and S. marcescens by cisplatin has been known for almost 45 years.2 In our initial tests, we confirmed the sensitivity of E. coli and S. marcescens to cisplatin. Table 1 shows such a test with E. coli strains 153z g, ZK 650 and C600 R1 and with S. marcescens. Our further experiments showed inhibition of E. coli strains ZY and ESS as well as P. aeruginosa. The effect of

Memories of a great man, Ivan Málek.

Abstract: Ivan Málek was a great scientist and an inspiration to Czech scientists and to microbiologists and biochemical engineers around the world. He brought Czech microbiology into the world of science and medicine. His devotion to continuous fermentation was recognized throughout the world. Despite the German occupation of Czechoslovakia during World War II, Málek worked on autovaccination therapy and was able to produce small amounts of penicillin, which was used to treat ill patients. He was a prolific writer of microbiological textbooks including Microbiology and Epidemiology (1946), Laboratory Methods for Bacteriological Diagnosis (1948), Fight of Modern Science Against Microorganisms (1951) and General Medical Microbiology (1953). It was in 1945 that, as a microbiologist and physician, he was appointed Lecturer at Charles University. A year after that, he went to Connaught Laboratories at the University of Toronto to study methods of penicillin production. This led to the establishment in 1949 of the first Czechoslovak penicillin factory in Roztoky u Prahy, a suburb of Prague. After his return from Canada, Málek lectured and taught more than 1,500 students studying medicine or nursing. In 1947, he established the country’s first school of medical laboratory technology. Málek became Associate Professor in 1948 and published his paper on variability of bacteria. In that same year, he taught and helped organize research at the new School of Medicine in Hradec Kralove. He also continued his work on continuous fermentation and returned to an early interest in mycobacteria. When the country formed an Academy of Sciences (ASCR) made up of research institutes in natural and social sciences in 1950, Málek was called upon to become the Director of the Central Institute of Biology in Prague and the Chairman of the Czechoslovak Society for Microbiology. He was soon elected to the ASCR and appointed as Chairman of the Central Institute of Biology. He helped found the journal Folia Microbiologica in 1956 and became the first Director of the Institute of Microbiology which was spun off from the Central Institute of Biology. This new institute, which soon became famous around the world for its first-rate research, was established in a new building in Krc, a district of Prague. He continued his work on continuous fermentation and established the importance of the ‘‘physiologic state’’ of microbiological populations. He was instrumental in the annual sending of ten or more Institute scientists to various laboratories in the USA and Western Europe. This is the way that many of us became familiar with excellent Czech scientists in our laboratories and those of our colleagues. Málek also arranged for foreign scientists to do their sabbatical leave research at the Institute of Microbiology. He was always willing to help the Institute’s scientists and technicians to overcome their difficult problems of life and existence. Quite often he served as an umbrella, kindly covering their more or less frequent acts of misconduct against an oppressive regime. Of great interest to Málek was the setting up of international meetings. After organizing the First International Symposium on the Continuous Cultivation of Microorganisms in Prague in 1958, the Proceedings were published by the ASCR and became well known around the world. This was followed by later Symposia in Prague in 1962, Porton Down, UK in 1966, Prague in 1968, and Oxford in A. L. Demain (&) Charles A. Dana Research Institute for Scientists Emeriti (RISE), Drew University, Madison, NJ 07940, USA e-mail: ademain@drew.edu