Gene Regulation

Excerpt

Even though components of important regulatory systems such as RpoS, which are essential for the general stress response in many bacteria, seem to be absent in H. pylori, this bacterium is clearly capable of mounting such a response. Two H. pylori genome sequences are currently available (2, 123), but insight into how gene expression is regulated is still limited. However, studies on several classical regulatory systems and on phase variation are slowly beginning to elucidate some aspects of gene regulation in H. pylori.

Because H. pylori shows responses to various environmental stresses for which the classical global regulators are absent, H. pylori must have alternative, yet unrecognized regulatory systems. One possible explanation is that the few classical transcriptional regulators that are present in H. pylori may provide additional functions, thereby compensating for lack of some regulators. The repressor HspR and possibly HrcA may constitute alternatives for the heat shock sigma factor σ³², as seems to be the case in C. jejuni (121, 122). The absence of the master regulator RpoS (42, 60, 76) may be compensated for by alternative regulator proteins such as Fur and HspR (12, 17, 114). In addition, it becomes more clear that phase variation plays an important role in H. pylori gene regulation, whereas mechanisms such as DNA methylation and supercoiling should be considered as potential factors affecting H. pylori gene transcription.

Obviously, much work remains to be done to elucidate the regulatory mechanisms that are involved in H. pylori gene expression. The application of novel techniques and approaches such as DNA microarrays and proteomics will hopefully lead to the identification of additional environmentally regulated genes, while further characterization of the two-component systems will give insight into how H. pylori responds to its environment and is able to cause disease. Surprisingly little is known about the in vivo relevance of gene regulation in H. pylori. The use of in vitro systems simulating in vivo conditions remains inadequate, so in vivo studies are required using techniques such as IVET (in vivo expression technology) or IVIAT (in vivo induced antigen technology) techniques (24, 55).

All bacteria, including H. pylori, sense their environment and respond to changing conditions by adjusting the level of expression of certain genes. Perhaps the paucity of regulatory functions in H. pylori makes the field of gene regulation an even more important subject for research. Targeting a regulatory pathway in such a background renders it more likely that vaccines or therapies will be efficient, as redundant pathways may not be present.