Role of AmiA in the Morphological Transition of Helicobacter pylori and in Immune Escape

PLoS Pathogens

Dominique Mengin-Lecreulx¹  Stephen E Girardin²  Catherine Werts³  Stéphanie Guadagnini⁴  Marie-Christine Prévost⁴  Nadège Cayet⁴  Chantal Ecobichon⁵  Catherine Chaput⁵  Ivo G Boneca⁵  Agnès Labigne⁵ 

[1] Enveloppes Bactériennes et Antibiotiques, UMR 8619 CNRS, Université Paris-Sud, Orsay, France;Groupe Avenir, INSERM U389, Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France;Groupe Immunité Innée et Signalisation, Institut Pasteur, Paris, France;Plate-Forme de Microscopie Électronique, Institut Pasteur, Paris, France;Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris, France

关键词: Helicobacter pylori;    Transcription factors;    Polymerase chain reaction;    Epithelial cells;    Oligonucleotides;    Plasmid construction;    Hydrolases;    Peptidoglycans;   

DOI  :  10.1371/journal.ppat.0020097

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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-β(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-κB 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.

【 授权许可】

CC BY