Vol.61 No.6 November 2013
Bacterial resistance mechanisms to oxyimino β-lactams and carbapenems on the basis of the β-lactamase structure
Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba, Japan
Abstract
Class A and C β-lactamases are similar in their entire three dimensional and active site structures, however their deacylation mechanisms are quite different. In the case of class A β-lactamases, deacylation water is positioned at the bottom of the active site pocket and attacks the carbonyl carbon of the substrate in an upward direction. On the other hand, the deacylation water of class C β-lactamases attacks the carbonyl carbon in a downward direction from the solvent. The difference is very important to understand the reaction mechanism of what we call "slow substrate" type β-lactams. Alternatively, the disease-causing bacteria are in an evolutionary rat-race with the new type of antibiotics. Oxyimino β-lactamases and carbapenems are widely used β-lactam antibiotics that resist hydrolysis by serine β-lactamases. Furthermore, extensive use of oxyimino β-lactams and carbapenems resulted in the emergence of ESBLs(Extended Spectrum β-lactamases) and carbapenemases, respectively. In this review, we discuss why oxyimino β-lactams and carbapenems resist hydrolysis by wild-type class A and C β-lactamases and why ESBLs and class A carbapenemases can hydrolyze them, respectively, on the basis of the difference in their deacylation mechanisms.
Key word
drug-resistance, oxyimino cephalosporin, carbapenem, extended spectrum β-lactamase
Received
August 1, 2013
Accepted
August 28, 2013
Jpn. J. Chemother. 61 (6): 479-491, 2013
