STRUCTURAL AND MECHANISTIC BASIS FOR THE O-ACETYLATION OF PEPTIDOGLYCAN BY THE VIRULENCE FACTORS PatB OF Neisseria gonorrhoeae AND OatA FROM BOTH Staphylococcus aureus AND Streptococcus pneumoniae.

摘要

The O-acetylation of the essential bacterial cell wall polymer peptidoglycan (PG) is known to occur in a large number of bacteria including many important human pathogens, such as Staphylococcus aureus, species of Enterococcus, Helicobacter pylori, Campylobacter jejuni, and Neisseria gonnorrhoeae.1 This modification to the C-6 position of N-acetylmuramoyl residues in PG inhibits the action of muramidases (lysozymes) of innate immune systems in a concentration dependent manner, and it totally precludes the activity of the lytic transglycosylases, bacterial autolysins that are involved with the insertion of flagella, pili, and secretion/transport systems, as well as the general biosynthesis and turnover of the PG sacculus. We have characterized two distinct two-component systems for PG O-acetylation in Gram-positive and Gram-negative bacteria, respectively. In Gram-negative bacteria, such as N. gonorrhoeae, an integral membrane protein, PG O-acetyltransferase (Pat) A, is proposed to translocate acetate from cytoplasmic pools of acetyl-CoA through the cytoplasmic membrane to the periplasm for its transfer to PG by PatB.2 With S. aureus, S. pneumoniae and other Gram-positive pathogens, a single protein, O-acetyltransferase (OatA), appears to be a fusion of PatA and PatB to catalyze both the translocation and transfer of acetyl groups for PG O-acetylation.3