Abstract
Persistent colonization of mucosal surfaces by bacteria in the mammalian host requires concerted expression of colonization factors, depending on the environmental conditions.
Helicobacter hepaticus
is a urease-positive pathogen that colonizes the intestinal and hepatobiliary tracts of rodents. Here it is reported that urease expression of
H. hepaticus
is iron repressed by the transcriptional regulator Fur. Iron restriction of growth medium resulted in a doubling of urease activity in wild-type
H. hepaticus
strain ATCC 51449 and was accompanied by increased levels of urease subunit proteins and
ureA
mRNA. Insertional inactivation of the
fur
gene abolished iron-responsive repression of urease activity, whereas inactivation of the
perR
gene did not affect iron-responsive regulation of urease activity. The iron-responsive promoter element was identified directly upstream of the
H. hepaticus ureA
gene. Recombinant
H. hepaticus
Fur protein bound to this
ureA
promoter region in a metal-dependent matter, and binding resulted in the protection of a 41-bp, Fur box-containing operator sequence located at positions −35 to −75 upstream of the transcription start site. In conclusion,
H. hepaticus
Fur controls urease expression at the transcriptional level in response to iron availability. This represents a novel type of urease regulation in ureolytic bacteria and extends the already diverse regulatory repertoire of the Fur protein.