Abstract
ABSTRACT
Phase variation is important in bacterial pathogenesis, since it generates antigenic variation for the evasion of immune responses and provides a strategy for quick adaptation to environmental changes. In this study, a
Helicobacter pylori
clone, designated MOD525, was identified that displayed phase-variable
lacZ
expression. The clone contained a transcriptional
lacZ
fusion in a putative type III DNA methyltransferase gene (
mod
, a homolog of the gene JHP1296 of strain J99), organized in an operon-like structure with a putative type III restriction endonuclease gene (
res
, a homolog of the gene JHP1297), located directly upstream of it. This putative type III restriction-modification system was common in
H. pylori
, as it was present in 15 out of 16 clinical isolates. Phase variation of the
mod
gene occurred at the transcriptional level both in clone MOD525 and in the parental
H. pylori
strain 1061. Further analysis showed that the
res
gene also displayed transcriptional phase variation and that it was cotranscribed with the
mod
gene. A homopolymeric cytosine tract (C tract) was present in the 5′ coding region of the
res
gene. Length variation of this C tract caused the
res
open reading frame (ORF) to shift in and out of frame, switching the
res
gene on and off at the translational level. Surprisingly, the presence of an intact
res
ORF was positively correlated with active transcription of the downstream
mod
gene. Moreover, the C tract was required for the occurrence of transcriptional phase variation. Our finding that translation and transcription are linked during phase variation through slipped-strand mispairing is new for
H. pylori
.