Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology

Scientific Reports
Ewa GraveHideaki Itoh

Abstract

Geranylgeranylacetone (GGA) is used to treat patients suffering from peptic ulcers and gastritis. We examined the effect of GGA on Helicobacter pylori, which is a causative factor of gastrointestinal diseases. Previously, we have reported that GGA binds specifically to the molecular chaperone HSP70. In this paper, we report that GGA bounds to H. pylori HSP70 (product of the DnaK gene) with 26-times higher affinity than to human HSP70, and induced large conformational changes as observed from surface plasmon resonance and circular dichroism. Binding of GGA suppressed the activity of the H. pylori chaperone. GGA also altered several characteristics of H. pylori cells. GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells. GGA also caused morphological alterations in H. pylori as reflected in fewer coccoid-like cells, suggesting that GGA converts H. pylori to an actively dividing, spiral state (vegetative form) from a non-growing, coccoid state. This morphological conversion by GGA resulted in accelerated growth of H. pylori. These results suggest a model in which GGA sensitizes H. pylori to antibiotic treatment by conve...Continue Reading

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Citations

Feb 13, 2016·Cell Stress & Chaperones·Jürgen Radons

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Methods Mentioned

BETA
biopsy
surface plasmon resonance
Circular Dichroism
environmental stresses
PCR
chips
chip
enzyme-linked immunosorbent assay

Software Mentioned

AnaeroPack
SSE
BIAcore
BIAevaluation

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