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

Grave E, Yokota S, Yamamoto S, Tamura A, Ohtaki-Mizoguchi T, Yokota K, Oguma K, Fujiwara K, Ogawa N, Okamoto T, Otaka M, Itoh H - Sci Rep (2015)

Bottom Line: GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.

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 converting the cells to an actively growing state.

No MeSH data available.


Related in: MedlinePlus

Effect of GGA on H. pylori cell morphology.H. pylori SS1 was cultured in BHI-FBS broth at 37 oC under microaerophilic condition in the absence or presence of GGA at a concentration of 0 (A), 1 (B), and 5 mM (C). Bacterial smear was stained by Gram staining. Coccoid form cells (D) were prepared by cultivation under anaerobic condition. Arrows in (A) indicate coccoid-like cells.
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f6: Effect of GGA on H. pylori cell morphology.H. pylori SS1 was cultured in BHI-FBS broth at 37 oC under microaerophilic condition in the absence or presence of GGA at a concentration of 0 (A), 1 (B), and 5 mM (C). Bacterial smear was stained by Gram staining. Coccoid form cells (D) were prepared by cultivation under anaerobic condition. Arrows in (A) indicate coccoid-like cells.

Mentions: In broth culture medium, GGA accelerated the growth of H. pylori in a dose-dependent manner (Fig. 5). Microscopic observation of the cells from these cultures revealed a mixture of Gram-negative rods and small spherical forms. A Gram stained micrograph of typical coccoid-form cells was shown in Fig. 6-D as a control. The coccoid-form cells were round and deeper pink than the rod-shaped cells. GGA caused a disappearance of coccoid-like form cells in a dose-dependent manner (Fig. 6). Therefore, GGA decreased the occurrence of the viable-but-not-culturable coccoid form, and increased highly-dividing rod-shaped cells in these cultures of H. pylori.


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

Grave E, Yokota S, Yamamoto S, Tamura A, Ohtaki-Mizoguchi T, Yokota K, Oguma K, Fujiwara K, Ogawa N, Okamoto T, Otaka M, Itoh H - Sci Rep (2015)

Effect of GGA on H. pylori cell morphology.H. pylori SS1 was cultured in BHI-FBS broth at 37 oC under microaerophilic condition in the absence or presence of GGA at a concentration of 0 (A), 1 (B), and 5 mM (C). Bacterial smear was stained by Gram staining. Coccoid form cells (D) were prepared by cultivation under anaerobic condition. Arrows in (A) indicate coccoid-like cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561889&req=5

f6: Effect of GGA on H. pylori cell morphology.H. pylori SS1 was cultured in BHI-FBS broth at 37 oC under microaerophilic condition in the absence or presence of GGA at a concentration of 0 (A), 1 (B), and 5 mM (C). Bacterial smear was stained by Gram staining. Coccoid form cells (D) were prepared by cultivation under anaerobic condition. Arrows in (A) indicate coccoid-like cells.
Mentions: In broth culture medium, GGA accelerated the growth of H. pylori in a dose-dependent manner (Fig. 5). Microscopic observation of the cells from these cultures revealed a mixture of Gram-negative rods and small spherical forms. A Gram stained micrograph of typical coccoid-form cells was shown in Fig. 6-D as a control. The coccoid-form cells were round and deeper pink than the rod-shaped cells. GGA caused a disappearance of coccoid-like form cells in a dose-dependent manner (Fig. 6). Therefore, GGA decreased the occurrence of the viable-but-not-culturable coccoid form, and increased highly-dividing rod-shaped cells in these cultures of H. pylori.

Bottom Line: GGA-treated cells elicited enhanced interleukin-8 production by gastric cancer cell lines and potentiated susceptibility to complement as compared to untreated cells.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, Graduate School and Faculty of Engineering Science, Akita University, Akita 010-8502, Japan.

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 converting the cells to an actively growing state.

No MeSH data available.


Related in: MedlinePlus