A new lipase as a pharmaceutical target for battling infections caused by Staphylococcus aureus: Gene cloning and biochemical characterization

Abstract

Staphylococcus aureus lipases along with other cell-wall-associated proteins and enzymes (i.e., catalase, coagulase, protease, hyaluronidase, and -lactamase) play important roles in the pathogenesis of S. aureus and are important subject of drug targeting. The appearance of antibiotic-resistant types of pathogenic S. aureus (e.g., methicillin-resistant S. aureus, MRSA) is a worldwide medical problem. In the present work, a novel lipase from a newly isolated MRSA strain from a cow with subclinical mastitis was cloned and biochemically characterized. The mature part of the lipase was expressed inEscherichia coli and purified by nickel affinity chromatography. It displays a high lipase activity at pH8.0 and 25 degrees C using p-nitrophenyl palmitate and has a preference for medium-long-chain substrates of p-nitrophenyl esters (pNPC10-C16). Furthermore, in search of inhibitors, the effect of farnesol on the growth of S. aureus and the lipase activity was also studied. Farnesol inhibits the growth of S. aureus and is a mixed-type inhibitor with K-i and K-i values of 0.2 and 1.2 mmolL(-1), respectively. A lipase with known properties could not only serve as a template for developing inhibitors for S. aureus but also a valuable addition to enzyme toolbox of biocatalysis. The discovery of this lipase can be potentially important and could provide a new target for pharmaceutical intervention against S. aureus infection. (C) 2014 International Union of Biochemistry and Molecular Biology, Inc.