The 3′-to-5′ Exoribonuclease (Encoded by HP1248) of Helicobacter pylori Regulates Motility and Apoptosis-Inducing Genes

Abstract

The human gastric pathogen Helicobacter pylori has many virulence factors involved in pathogenesis, but the mechanisms regulating these virulence factors are not yet fully understood. In this study, we cloned HP1248, which is similar in sequence to Escherichia coli vacB , which was previously shown to be associated with the expression of virulence in Shigella and enteroinvasive E. coli. E. coli vacB encodes RNase R. RNase R is involved in the posttranscriptional regulation of mRNA stability. By global transcriptional microarray profiling of an H. pylori HP1248 deletion mutant, we defined six virulence-related genes which were posttranscriptionally downregulated by HP1248, including the motility-related genes HP1192 and flaB , the chemotaxis-related gene cheY , and the apoptosis-inducing genes HP0175, cagA , and gtt . In this study, recombinant HP1248 protein expressed in E. coli showed 3′-to-5′ exoribonuclease activity. Motility and apoptosis induction were increased in the H. pylori HP1248 deletion mutant. We also showed that HP1192 is associated with H. pylori motility, possibly through HP1248 regulation. Further, we suggested and studied the possible mechanisms of this specific regulation of virulent genes by HP1248. In addition, the expression level of HP1248 mRNA changed dramatically in response to a variety of altered environmental conditions, including pH and temperature. Hence, HP1248 in H. pylori seems to play a role in environmental sensing and in regulation of virulent phenotypes, such as motility and host apoptosis induction.