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Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape.

Chaput C, Ecobichon C, Cayet N, Girardin SE, Werts C, Guadagnini S, Prévost MC, Mengin-Lecreulx D, Labigne A, Boneca IG - PLoS Pathog. (2006)

Bottom Line: Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms.PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-kappaB activation in epithelial cells.Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection.

View Article: PubMed Central - PubMed

Affiliation: Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France.

ABSTRACT
The human gastric pathogen Helicobacter pylori is responsible for peptic ulcers and neoplasia. Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms. The molecular mechanisms of the morphological transition between these two forms and the role of coccoids remain largely unknown. The peptidoglycan (PG) layer is a major determinant of bacterial cell shape, and therefore we studied H. pylori PG structure during the morphological transition. The transition correlated with an accumulation of the N-acetyl-D-glucosaminyl-beta(1,4)-N-acetylmuramyl-L-Ala-D-Glu (GM-dipeptide) motif. We investigated the molecular mechanisms responsible for the GM-dipeptide motif accumulation, and studied the role of various putative PG hydrolases in this process. Interestingly, a mutant strain with a mutation in the amiA gene, encoding a putative PG hydrolase, was impaired in accumulating the GM-dipeptide motif and transforming into coccoids. We investigated the role of the morphological transition and the PG modification in the biology of H. pylori. PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-kappaB activation in epithelial cells. Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection.

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Effect of Amoxicillin on H. pylori MorphologySEM of H. pylori strain 26695 (A and B) and its isogenic amiA mutant (C and D) grown without amoxicillin (A and C) and after 3–4 h exposure to 10 μg/ml amoxicillin (B and D). Amoxicillin treatment of the amiA mutant bypasses the requirement of amiA for the morphological transition, indicating that absence of coccoid forms was not due to sterical hindrance of the bacterial chains.
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ppat-0020097-g003: Effect of Amoxicillin on H. pylori MorphologySEM of H. pylori strain 26695 (A and B) and its isogenic amiA mutant (C and D) grown without amoxicillin (A and C) and after 3–4 h exposure to 10 μg/ml amoxicillin (B and D). Amoxicillin treatment of the amiA mutant bypasses the requirement of amiA for the morphological transition, indicating that absence of coccoid forms was not due to sterical hindrance of the bacterial chains.

Mentions: Some stress signals, including amoxicillin treatment, can induce the morphological transition into coccoid forms [4]. We investigated the response of the amiA mutant to amoxicillin. First, we determined the minimum inhibitory concentration (MIC) of amoxicillin: it was identical for the amiA mutant and the parental strain 26695 (0.06 μg/ml). After overnight culture, 10 μg/ml amoxicillin was added to the medium, and after 3 h of antibiotic treatment, bacteria were observed using SEM. The amiA mutant formed chains of spherical bacteria (Figure 3), rod-shaped bacteria, and, most frequently, both rod-shaped and spherical bacteria. Thus, the impaired morphological transition is not an artifact and does not result from steric hindrance of bacterial chain formation (see Table 1 for quantification). Therefore, AmiA is required both for PG modifications and for the morphological transition.


Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape.

Chaput C, Ecobichon C, Cayet N, Girardin SE, Werts C, Guadagnini S, Prévost MC, Mengin-Lecreulx D, Labigne A, Boneca IG - PLoS Pathog. (2006)

Effect of Amoxicillin on H. pylori MorphologySEM of H. pylori strain 26695 (A and B) and its isogenic amiA mutant (C and D) grown without amoxicillin (A and C) and after 3–4 h exposure to 10 μg/ml amoxicillin (B and D). Amoxicillin treatment of the amiA mutant bypasses the requirement of amiA for the morphological transition, indicating that absence of coccoid forms was not due to sterical hindrance of the bacterial chains.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1574363&req=5

ppat-0020097-g003: Effect of Amoxicillin on H. pylori MorphologySEM of H. pylori strain 26695 (A and B) and its isogenic amiA mutant (C and D) grown without amoxicillin (A and C) and after 3–4 h exposure to 10 μg/ml amoxicillin (B and D). Amoxicillin treatment of the amiA mutant bypasses the requirement of amiA for the morphological transition, indicating that absence of coccoid forms was not due to sterical hindrance of the bacterial chains.
Mentions: Some stress signals, including amoxicillin treatment, can induce the morphological transition into coccoid forms [4]. We investigated the response of the amiA mutant to amoxicillin. First, we determined the minimum inhibitory concentration (MIC) of amoxicillin: it was identical for the amiA mutant and the parental strain 26695 (0.06 μg/ml). After overnight culture, 10 μg/ml amoxicillin was added to the medium, and after 3 h of antibiotic treatment, bacteria were observed using SEM. The amiA mutant formed chains of spherical bacteria (Figure 3), rod-shaped bacteria, and, most frequently, both rod-shaped and spherical bacteria. Thus, the impaired morphological transition is not an artifact and does not result from steric hindrance of bacterial chain formation (see Table 1 for quantification). Therefore, AmiA is required both for PG modifications and for the morphological transition.

Bottom Line: Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms.PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-kappaB activation in epithelial cells.Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection.

View Article: PubMed Central - PubMed

Affiliation: Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France.

ABSTRACT
The human gastric pathogen Helicobacter pylori is responsible for peptic ulcers and neoplasia. Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms. The molecular mechanisms of the morphological transition between these two forms and the role of coccoids remain largely unknown. The peptidoglycan (PG) layer is a major determinant of bacterial cell shape, and therefore we studied H. pylori PG structure during the morphological transition. The transition correlated with an accumulation of the N-acetyl-D-glucosaminyl-beta(1,4)-N-acetylmuramyl-L-Ala-D-Glu (GM-dipeptide) motif. We investigated the molecular mechanisms responsible for the GM-dipeptide motif accumulation, and studied the role of various putative PG hydrolases in this process. Interestingly, a mutant strain with a mutation in the amiA gene, encoding a putative PG hydrolase, was impaired in accumulating the GM-dipeptide motif and transforming into coccoids. We investigated the role of the morphological transition and the PG modification in the biology of H. pylori. PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-kappaB activation in epithelial cells. Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection.

Show MeSH
Related in: MedlinePlus