The Helicobacter pylori sialic acid binding adhesin SabA is regulated via a network of two-component systems
(English)Manuscript (preprint) (Other academic)
The acid-responsive signaling system ArsRS plays a key role in regulating factors important for survival in acidic conditions during infection of the human stomach by Helicobacter pylori. In addition, ArsRS was suggested to control the disease-associated attachment protein SabA, however, mechanistic data is still lacking. We show that the repressing effect of the ArsRS system on SabA expression occurs both at acidic and neutral conditions and is mediated at the transcriptional level. Purified His6-ArsR binds PsabA DNA at several sites, with varying affinity and independent of phosphorylation status and H. pylori strains showed unique cognate PsabA sequences to tweak the ArsR binding ability, resulting in strain-dependent repression of SabA expression. By site-directed mutagenesis we reveal key amino acids for the binding activity of ArsR. Finally, we show that that ArsR binds to A/T-rich DNA as dimers or larger multimers, suggesting that ArsR has affinity for DNA structures rather than to a specific promoter DNA sequence. SabA expression is further influenced by the FlgRS and CrdRS two-component systems, illustrating a complicated crosstalk among regulatory networks in H. pylori.
Microbiology in the medical area
Research subject Medical Biochemistry
IdentifiersURN: urn:nbn:se:umu:diva-120293OAI: oai:DiVA.org:umu-120293DiVA: diva2:928083
FunderSwedish Research Council, K2009-56X-20037-04-3 (VR/NT)Swedish Cancer Society, 09 0641The Kempe Foundations