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1

Phage therapy: a reappraisal of bacteriophages as antibiotics

100%
Inal J. M.
Archivum Immunologiae et Therapiae Experimentalis
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2003
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vol. 51
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issue 4
237-244
EN
The concept of phage therapy to treat bacterial infections was born with the discovery of bacteriophage almost a century ago. After a chequered history its current renaissance is fuelled by the dangerous appearance of antibiotic-resistant bacteria on a global scale. As a mark of this renewed interest, the unanswered problems of phage therapy are now being addressed, especially for human use. Phage therapy in agricultural, food processing and fish farming industries is already successful and this review, whilst being aware of the potential drawbacks, emphasizes the need for further carefully controlled empirical data on its efficacy and safety in treating human and animal disease, especially in view of its numerous advantages over antibiotics. Finally the potential of phage therapy against bioterrorism and the emergence of second generation phage antibacterials based on phage-derived single-protein lysis systems are addressed.
2

Bacteriophage contamination: is there a simple method to reduce its deleterious effects in laboratory cultures and biotechnological factories?

100%
Los M., Czyz A., Sell E., Wegrzyn A., Neubauer P., Wegrzyn G.
Journal of Applied Genetics
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2004
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vol. 45
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issue 1
111-120
EN
Infection of bacterial cultures by bacteriophages as well as prophage induction in the host cells are serious problems in both research and biotechnological laboratories. Generally, prevention strategies (like good laboratory/factory hygiene, sterilisation, decontamination and disinfection) are necessary to avoid bacteriophage contamination. However, it is well known that no matter how good the laboratory/factory practice and hygiene are, bacteriophage infections occur from time to time. The use of immunised or resistant bacterial strains against specific phages may be helpful, but properties of the genetically modified strains resistant to phages are often worse (from the point of view of a researcher or a biotechnological company) than those of the parental, phage-sensitive strains. In this article we review recent results that may provide a simple way to minimise deleterious effects of bacteriophage infection and prophage induction. It appears that low bacterial growth rates result in a significant inhibition of lytic development of various bacteriophages. Moreover, spontaneous prophage induction is less frequent in slowly growing bacteria.
3

The minimal genome paradox

88%
Wegrzyn G.
Journal of Applied Genetics
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2001
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vol. 42
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issue 3
385-392
EN
The concept of a ?minimal genome? has appeared as an attempt to answer the question what the minimum number of genes or minimum amount of DNA to support life is. Since bacteria are cells bearing the smallest genomes, it has been generally accepted that the minimal genome must belong to a bacterial species. Currently the most popular chromosome in studies on a minimal genome belongs to Mycoplasma genitalium, a parasite bacterium whose total genetic material is as small as 580 kb. However, the problem is how we define life, and thus also a minimal genome. M. genitalium is a parasite and requires substances provided by its host. Therefore, if a genome of a parasite can be considered as a minimal genome, why not to consider genomes of bacteriophages? Going further, bacterial plasmids could be considered as minimal genomes. The smallest known DNA region playing the function of the origin of replication, which is sufficient for plasmid survival in natural habitats, is as short as 32 base pairs. However, such a small DNA molecule could not form a circular form and be replicated by cellular enzymes. These facts may lead to an ostensibly paradoxical conclusion that the size of a minimal genome is restricted by the physical size of a DNA molecule able to replicate rather, than by the amount of genetic information.
4

DNA libraries ? a way to understand genome structure

88%
Wolko L., Slomski R.
Biotechnologia
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2003
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issue 3
159-179
EN
Wide genome physical mapping is becoming a main goal of current genomic research on many plant and animal species. It provides essential basis for large-scale genome sequencing, but requires well-saturated large-insert DNA genomic libraries. This review presents a progress in the construction and application of genomic libraries. New trends towards the improvement of cloning vectors and adjustment to new tasks of molecular genetics are also presented.
5

Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers

75%
Sinkovics J. G., Horvath J. C.
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|
issue 6
3-59
EN
Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a combination of naturally oncolytic viruses and wild-type viruses rendered oncolytic and harmless by genetic engineering, that will induce complete remissions of human tumors. It may be necessary to co-administer certain chemotherapeutic agents, advanced cancer vaccines, or even immune lymphocytes, and targeted therapeuticals, to ascertain, that remissions induced by the viral agents will remain complete and durable; will co-operate with anti-tumor host immune reactions, and eventually will result in cures of advanced metastatic human cancers. Key words: naturally oncolytic viruses viral oncolysates, human cancer immunity, interaction of resident viral flora with the oncolytic virus, oncosuppressive bacteriophages, genetically engineered oncolytic viruses .
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