The CrdRS two‐component system in H elicobacter pylori responds to nitrosative stress

Summary H elicobacter pylori inhabits the gastric mucosa where it senses and responds to various stresses via a two‐component systems ( TCS s) that enable its persistent colonization. The aim of this study was to investigate whether any of the three paired TCS s ( A rs RS , F le RS and C rd RS ) in H . pylori respond to nitrosative stress. The results showed that the expression of crdS was significantly increased upon exposure to nitric oxide ( NO ). crd S ‐knockout (Δ crd S ) and crd R / crd S ‐knockout (Δ crd RS ) H . pylori , but not ars S ‐knockout (Δ ars S ) or fle S ‐knockout (Δ fle S ) H . pylori , showed a significant loss of viability upon exposure to NO compared with wild‐type strain. Knockin crd S (Δ crd S ‐in ) significantly restored viability in the presence of NO . Global transcriptional profiling analysis of wild‐type and Δ crd S H . pylori in the presence or absence of NO showed that 101 genes were differentially expressed, including copper resistance determinant A ( crd A ), transport, binding and envelope proteins. The C rd R binding motifs were investigated by competitive electrophoretic mobility shift assay, which revealed that the two AC ‐rich regions in the crd A promoter region are required for binding. These results demonstrate that C rd R – crdA interaction enables H . pylori to survive under nitrosative stress.