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.
