Why is peptidoglycan important for distinguishing bacteria from archaea?

Peptidoglycan is a critical marker for distinguishing between bacteria and archaea because it is a structural component found almost exclusively in the cell walls of bacteria, whereas it is entirely absent in archaea.12

In bacteria, peptidoglycan (also known as murein) forms a rigid, meshlike layer that provides shape and stability to the cell. Because this molecule is unique to the bacterial domain, it serves as a primary biochemical boundary between these two groups of prokaryotes.12

While some archaea possess wall materials that may superficially resemble peptidoglycan, they differ fundamentally in their chemical composition—for instance, using talosaminuronic acid instead of the muramic acid found in bacterial peptidoglycan. Furthermore, because archaea lack true peptidoglycan, they are naturally resistant to many antimicrobial agents, such as penicillin and lysozyme, which specifically target and disrupt the peptidoglycan synthesis or structure in bacteria.1