Sortases make pili from three ingredients

Abstract

Many bacterial pathogens have evolved hair-like extensions that project from their surfaces and enable adhesion to host tissues, formation of biofilms, motility, and even transfer of genetic material (1). Gram-positive bacteria use sortases, membrane-anchored transpeptidases, to cleave precursor proteins at cognate recognition motifs within C-terminal sorting signals and assemble pili in their cell wall envelope (2, 3). The transient product of this reaction is an acyl enzyme that, depending on the sortase involved, is relieved by a specific nucleophile (4). Currently studied sortases accept only one nucleophile to complete their transpeptidation reaction (5–8). For example, sortase A of Staphylococcus aureus forms an acyl enzyme with surface proteins bearing LPXTG motif sorting signals, which are subsequently relieved by the nucleophilic attack of the amino group of lipid II, the precursor of peptidoglycan synthesis in bacteria (9, 10). In this issue of PNAS, Mandlik et al. (11) provide new insight into sortases and their complicated recipes for pilus assembly.