Pardon the interruption: how Und-P sequestration has reshaped our understanding of the bacterial cell envelope

The bacterial cell envelope is composed of glycans that maintain cell shape and protect against antibiotics, immune systems, and other environmental hazards. The glycans found in the envelopes of most bacteria are assembled on and transported by the essential lipid carrier undecaprenyl phosphate (Und-P). Und-P is activated for glycan assembly by the dephosphorylation of undecaprenyl pyrophosphate (Und-PP), both during de novo synthesis and after Und-PP is released from glycan intermediates. Und-P sequestration occurs when Und-P cannot release from glycan precursors or Und-P(P)-binding compounds. Importantly, cells that cannot recycle Und-P produce too few cell wall precursors to sustain growth and will eventually lyse. This review summarizes the Und-P sequestration narrative, from its sporadic observation to its eventual mechanistic understanding. More broadly, deciphering Und-P sequestration has reshaped how we interpret phenotypes, uncover mechanisms of envelope assembly, and determine the activity of antibacterials. The far-reaching implications of these findings suggest that continued study of Und-P sequestration will not only yield a deeper understanding of the bacterial cell envelope but also reveal new strategies to disrupt this protective barrier.