Salmonella enterica is an intracellular bacterial pathogen that survives and proliferates inside phagocytic and non-phagocytic eukaryotic cells as part of its natural infection cycle. We are interested in deciphering the mechanisms that this pathogen exploits to establish long-lasting persistent infections within eukaryotic vacuolar compartments. We recently discovered that this pathogen controls bacterial progeny by triggering a unique autophagy process involving aggregation of host cell endo-membranes. Our current aim is to dissect envelope alterations that take place in intracellular Salmonella and, more specifically, changes in the peptidoglycan (PG) structure that may facilitate a prolonged persistent infection. We have also collected data supporting changes in the PG enzymatic machinery used by Salmonella once it colonizes the phagosomal compartment. Some of the PG enzymes up-regulated by Salmonella in the phagosome have evolved to act exclusively in this acidic environment and are encoded by genes absent in genomes of non-pathogenic bacteria. These observations support the idea of a dedicated subset of PG enzymes that might promote Salmonella adaptation to the intra‑phagosomal lifestyle. This group of ‘specialized’ PG enzymes therefore represent new attractive targets to combat intracellular bacterial infections.