Dual Protective Functions of Helicobacter pylori Peptidoglycan Modifications Impact Early and Late Survival in the Host

Structural motifs inherent in bacterial peptidoglycan (PG) are important recognition domains for some efficient host responses to pathogenic bacterial infection, so PG modifications by the infecting bacterium can neutralize host responses. Helicobacter pylori contain two PG modification enzymes, an N-deacetylase (PgdA) and an O-acetyltransferase (PatAB), but some naturally occurring strains lack the latter. Here the lysozyme resistance and the survival in both macrophages and in lysozyme deficient mice were studied for various H. pylori strains. Resistance to lysozyme killing of H. pylori was conferred by PgdA in naturally-occurring strains that lacked PatA (e.g. B128); the lysozyme sensitivity for B128 pgdA mutant was at the same level as that of a double mutant (pgdA patA) version within parent strain X47. Both PgdA- and PatAmediated PG modifications are important to H. pylori survival within macrophages. Mouse studies connected the lysozyme and macrophage results to the in vivo condition, in which lysozyme effects are expected early and cytokine production later, pertaining to specific host recognition events. An increased host lysozyme killing effect associated with the double