Peptidoglycan recycling in the Gram-positive bacterium Staphylococcus aureus and its role in host-pathogen interaction

Bacteria are enclosed by a peptidoglycan sacculus, an exoskeleton-like polymer composed of glycan strands cross-linked by short peptides. The sacculus surrounds the cell in a closed bag-like structure and forms the main structural component of the bacterial cell wall. As bacteria grow and divide, cell wall remodelling by peptidoglycan hydrolases results in the release of peptidoglycan fragments from the sacculus. In Gram-negative bacteria, these fragments are efficiently trapped and recycled. Gram-positive bacteria however shed large quantities of peptidoglycan fragments into the environment. For nearly five decades, Gram-positive bacteria were thus assumed not to recycle peptidoglycan and this process has remained enigmatic until recently. In this thesis, the occurrence and physiological role of peptidoglycan recycling in the Gram-positive pathogen Staphylococcus aureus was investigated. S. aureus is an important pathogen, and is becoming increasingly resistant to many antibiotics. Through bioinformatic and experimental means it was determined that S. aureus may potentially recycle components of peptidoglycan and novel peptidoglycan recycling components were identified and characterised. Though disruption of putative peptidoglycan recycling in S. aureus appears not affect growth or gross morphology of this bacterium, potential roles for peptidoglycan recycling in cell wall homeostasis and in virulence were identified. This is to my knowledge the first demonstration of a potential role of peptidoglycan recycling in either of these aspects of bacterial physiology in any Gram-positive bacterium. This is an important step forward in understanding the basic biology of Gram-positive bacteria, and in understanding the mechanisms of virulence in S. aureus. Future study of this process in S. aureus and other Gram-positive bacteria promises to reveal yet further facets of this process and its functions, potentially leading to the identification of novel therapeutic approaches to combat infections.