Geranylgeranylacetone selectively binds to the HSP70 of Helicobacter pylori and alters its coccoid morphology.
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 converting the cells to an actively growing state.
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Ewa
E
Grave
Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
Shin-ichi
S
Yokota
Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
Soh
S
Yamamoto
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Arisa
A
Tamura
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Takako
T
Ohtaki-Mizoguchi
Graduate School of Health Sciences, Okayama University, Okayama 700-8558, Japan.
Kenji
K
Yokota
Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Keiji
K
Oguma
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Kazuhiko
K
Fujiwara
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Nobuaki
N
Ogawa
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Tomoya
T
Okamoto
Department of Gastroenterology, Juntendo University School of Medicine, Bunkyo-Ku, Tokyo 113-8421, Japan.
Michiro
M
Otaka
Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.
Hideaki
H
Itoh
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000378:metabolism* / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins; D020349:Surface Plasmon Resonance
D001426:Bacterial Proteins; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; C031049:geranylgeranylacetone