Iron-responsive repression of urease expression in Helicobacter hepaticus is mediated by the transcriptional regulator Fur.
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.
Belzer
Clara
C
Department of Gastroenterology and Hepatology, Erasmus MC--University Medical Center, 3015 CE Rotterdam, The Netherlands.
van Schendel
Bart A M
BA
Kuipers
Ernst J
EJ
Kusters
Johannes G
JG
van Vliet
Arnoud H M
AH
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D018983:DNA Footprinting; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D044923:Helicobacter hepaticus / Q000201:enzymology* / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012329:RNA, Bacterial / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D024363:Transcription Initiation Site; D014510:Urease / Q000096:biosynthesis* / Q000235:genetics
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C068477:ferric uptake regulating proteins, bacterial; C122138:peroxide repressor proteins; D007501:Iron; D014510:Urease