Structural basis for antibiotic resistance by chloramphenicol acetyltransferase type A in Staphylococcus aureus

The authors solved the first crystal structure of the enzyme chloramphenicol acetyltransferase 1 (saCAT1) from Staphylococcus aureus, showing how the enzyme binds and modifies the antibiotic chloramphenicol (by acetylation) to prevent it from attaching to the bacterial ribosome, thereby rendering the drug ineffective. They detail key active‐site residues and measure kinetic parameters (Km ~ 16.9 µM for chloramphenicol; Ki ~ 83.7 µM for the inhibitor fusidic acid), highlighting that the inhibitor’s effect is limited and pointing to the enzyme structure as a foundation for designing new inhibitors or therapies to counteract this resistance mechanism.