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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 serum sensitivity of H. pylori cells.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were treated with 50% normal rabbit serum as a source of complement. After incubation at various times, the suspension was diluted appropriately and plated on sheep blood agar plates. After 72 h culture, the colonies were counted. Each experiment was performed in quadruplicate.
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f7: Effect of GGA on serum sensitivity of H. pylori cells.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were treated with 50% normal rabbit serum as a source of complement. After incubation at various times, the suspension was diluted appropriately and plated on sheep blood agar plates. After 72 h culture, the colonies were counted. Each experiment was performed in quadruplicate.

Mentions: The changes of cell morphology suggest that cell surface of H. pylori may be altered by GGA treatment. So we examined effect of GGA treatment on serum sensitivity, namely antibody-independent complement-mediated killing, by using normal rabbit serum as a source of complement. GGA-treated H. pylori cells were more rapidly killed by the serum than untreated cells (Fig. 7), consistent with the GGA-treated cells being more susceptible to complement.


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 serum sensitivity of H. pylori cells.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were treated with 50% normal rabbit serum as a source of complement. After incubation at various times, the suspension was diluted appropriately and plated on sheep blood agar plates. After 72 h culture, the colonies were counted. Each experiment was performed in quadruplicate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Effect of GGA on serum sensitivity of H. pylori cells.H. pylori SS1 was precultured in the absence or presence of GGA at a concentration of 0 (open circle), 1 (closed red diamond), and 5 (closed black square) mM. The resulting cells were treated with 50% normal rabbit serum as a source of complement. After incubation at various times, the suspension was diluted appropriately and plated on sheep blood agar plates. After 72 h culture, the colonies were counted. Each experiment was performed in quadruplicate.
Mentions: The changes of cell morphology suggest that cell surface of H. pylori may be altered by GGA treatment. So we examined effect of GGA treatment on serum sensitivity, namely antibody-independent complement-mediated killing, by using normal rabbit serum as a source of complement. GGA-treated H. pylori cells were more rapidly killed by the serum than untreated cells (Fig. 7), consistent with the GGA-treated cells being more susceptible to complement.

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