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Category: Bacterial Pathogenesis
Mutagenesis, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818005/9781555812133_Chap30-1.gif /docserver/preview/fulltext/10.1128/9781555818005/9781555812133_Chap30-2.gifAbstract:
The first part of this chapter gives a general background on mutagenesis, discusses how the appearance of spontaneous mutations within the chromosome of Helicobacter pylori is important for the dissemination of factors important in virulence and antibiotic resistance, and presents recent evidence for functional DNA repair systems thought to be absent in this organism. Induced mutagenesis has been pivotal in unravelling the pathophysiology of H. pylori. The second part of the chapter describes the techniques that have been employed, starting from the first reports of chemically induced mutations to the modern systematic approaches that will allow genome-wide analysis of the organism. There are three main categories of mutations: substitutions, frameshifts, and genomic rearrangements. Any bacterial cell contains various DNA repair systems, which protect against both spontaneous errors of replication and the mutagenic effects of chemical and physical agents generated from their own metabolism or the environment. Resistance to metronidazole is associated with loss of oxygen-insensitive NADPH nitroreductase activity, an enzyme that reduces metronidazole to active metabolites that are directly toxic to the bacterium. The genetic polymorphism of H. pylori was exemplified by a study that found that the nucleotide sequence of a 294-bp fragment of glmM (a housekeeping gene encoding a phosphoglucosamine mutase present in all strains) was unique for each of the 29 strains studied. In conclusion, the relatively recent development of molecular tools that allow site-directed mutagenesis, random mutagenesis, and systematic gene inactivation will greatly facilitate the genetic analysis of H. pylori.
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