UNRAVELING THE SIGNIFICANCE OF CLASS A SERINE β LACTAMASE PSE-4 TO CONFRONT ANTI-MICROBIAL RESISTANCE

Abstract

β -Lactamases are an important group of clinically significant enzymes that hydrolyze the β lactam antibiotics' four-membered ring. The Penicillinase group of enzymes is reported as the first ever β-lactamases discovered. Over time, spontaneous mutations in these enzymes have resulted in the generation of a large number of natural variants. These natural variants are known to have a wider resistance profile and hence are responsible for causing deadlier cases of MDR infections around the globe. Carbenicillinase is a penicillinase derivative group of enzymes that mostly hydrolyses carbenicillin. The first isolated carbenicillinase was known as CARB-1, which is also known as PSE-4. Currently, there are more than 100 reported natural variants of PSE-4, which plays a pivotal role in Pseudomonas’ resistance mechanism against commonly used drugs and drug-inhibitor combinations. In this report, we study the wild-type PSE-4 β-lactamase enzyme and characterize its biological attributes that would eventually contribute to the development of new-generation therapeutics, mitigating its devastating effects in the global clinical scenario. Apart from that, the PSE-4 E166A mutant is designed, expressed, and purified in understanding the role of Glu 166 residue in the catalysis of the SBL.