Surface proteins of Gram-positive bacteria are linked to the bacterial cell
wall by a mechanism that involves cleavage of a conserved Leu-Pro-X-Thr-Gl
y (LPXTG) motif and that occurs during assembly of the peptidoglycan cell w
all. A Staphylococcus aureus mutant defective in the anchoring of surface p
roteins was isolated and shown to carry a mutation in the srtA gene. Overex
pression of srtA increased the rate of surface protein anchoring, and homol
ogs of srtA were found in other pathogenic Gram-positive bacteria. The prot
ein specified by srtA, sortase, may be a useful target for the development
of new antimicrobial drugs.