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In August 1997 the complete annotated genome sequence ofHelicobacter pylori was published,1 just 15 years after the organism was first cultured.2 This is an important milestone in gastroenterology research as H pylori is the first enteropathogen to be fully sequenced. The availability of a complete genetic data set heralds a new era inH pylori research as it will provide a framework for global studies of virulence and other aspects of the organism’s biology. In this article we outline the genomics approaches that can now be applied and highlight the potential practical benefits of this research in terms of eradication therapy and disease prevention.
The H pylori genome sequence: new opportunities
Scientists at The Institute for Genomic Research (TIGR) (http://www.tigr.org) have determined the order of the 1 667 867 nucleotides that constitute the circular chromosomal content of H pylori strain ACTC 26695.1 Initial computer analysis suggests the presence of 1590 open reading frames (ORFs or genes), of which nearly 70% can be matched to genes encoding proteins of known function. This immense achievement gives us unequalled opportunities to relate gene sequence to biology and will provide insight into many aspects of the organism’s biology, such as replication, DNA repair, metabolism, ion and protein transport, cell wall structure, and virulence. The most intriguing findings are as follows:
Almost one third of the predicted coding sequences are ORFans—that is, they have no known homologues or any clues as to function. These ORFans may encode proteins unique to H pylori and provide selective targets for antibiotic therapy.
Very few regulatory proteins were found—by contrast to the Escherichia colisequence,3 10-fold less regulatory sequences have been identified. Tight regulation of gene expression is imperative for enteropathogenic bacteria whether they are continually responding to the harsh acidic environment of the stomach or bile salts in the intestine. …