Compositional analysis of bacterial peptidoglycan: insights from peptidoglycomics into structure and function

Peptidoglycan (PG) is a critical component of bacterial cell walls that stabilizes the cell membrane while performing diverse physiological roles. It consists of a polysaccharide backbone cross-linked by peptide side chains forming a lattice-like sacculus that encases the entire cell. The fundamental structural component known as a muropeptide is well characterized, although modifications to this structure are common and often linked to specific physiological functions. Recent advancements in mass spectrometry and bioinformatics now facilitate a detailed examination of the global composition of this essential biopolymer. We can deepen our understanding of its dynamic roles by employing peptidoglycomics to analyze how PG composition changes in response to physiological or environmental stimuli. This minireview will discuss the key physiological functions of peptidoglycan, introduce the peptidoglycomic approach, and highlight research where an omics-based perspective could significantly benefit future studies. By enabling a comprehensive, sensitive, and non-biased detection of PG modifications, peptidoglycomics provides a powerful lens to uncover novel structural variants and functional insights that were previously inaccessible using classical methodologies.