Fur functions as an activator and as a repressor of putative virulence genes in Neisseria meningitidis.
Fur is a well-known iron-responsive repressor of gene transcription, which is used by many bacteria to respond to the low-iron environment that pathogens encounter during infection. Four promoters of Neisseria meningitidis predicted to have Fur-binding boxes were selected to study the molecular interactions between Fur and the promoter regions of genes expected to play a central role in survival and pathogenesis. We demonstrate that Fur acts not only as a repressor, but also as an activator of gene expression both in vivo and in vitro. We report that Fur binds to operators located upstream of three promoters that are positively regulated in vivo by Fur and iron, whereas Fur binds to an operator overlapping the classically iron-repressed tbp promoter. Deletion of the upstream operator in the norB promoter abolished activation of transcription in vivo in response to iron and in vitro in response to Fur. The role of such a dual mechanism of Fur regulation during infection is discussed.
Delany
Isabel
I
Biochemistry and Molecular Biology Unit, IRIS, Chiron S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
Rappuoli
Rino
R
Scarlato
Vincenzo
V
D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D018983:DNA Footprinting; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics* / Q000472:pathogenicity*; D009875:Operator Regions, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D037521:Virulence Factors; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron