Mutagenesis

Excerpt

Helicobacter pylori has adapted to survive within the human stomach, an environment that is bathed in toxic agents generated from the bacterium's own metabolism and the host inflammatory response as well as other defenses of the host. Analysis of the two genome sequences of H. pylori (4, 61) has suggested that certain DNA repair systems, such as components of the mismatch repair system, are absent in this species. It is thought that the persistent accumulation of mutations within the genome may make an important contribution to the extraordinary genetic diversity of H. pylori and allow adaptation to new environmental challenges within the stomach (40, 57, 66).

In the first part of this chapter, we will give a general background on mutagenesis, discuss how the appearance of spontaneous mutations within the chromosome of H. pylori is important for the dissemination of factors important in virulence and antibiotic resistance, and present 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 will describe the techniques that have been employed, starting from the first reports of chemically induced mutations to the modern systematic approaches that will allow genomewide analysis of the organism.