Abstract
Carboxylesterases, historically referred as non-specific esterases, are ubiquitous hydrolases with high catalytic efficiency. Without exceptions, all mammalian species studied contain multiple forms of carboxylesterases. While having been widely studied in humans and experimental animals, these enzymes remain to be characterized in farm animals. In this study, we showed that pig liver esterase 1 (PLE1) and pig liver esterase 6 (PLE6) were highly active toward amoxicillin (AMO) and ampicillin (AMP), two major antibiotics that are widely used in food-supplements. Mass-spectrometric analysis established that the hydrolysis occurred at the β-lactam amide bond and the hydrolysis drastically decreased or completely eliminated the antibacterial activity. Furthermore, hydrolytic activity and proteomic analysis suggested that trace PLEs existed in pig plasma and contributed little to the hydrolysis of AMO and AMP. These results suggested that carboxylesterases-based hydrolysis determines the therapeutic intensity of these and related antibiotics and the magnitude of the determination occurs in a species-dependent manner.
Highlights
The widespread use of antibiotic supplements in farm animals is a major contributing factor to drug residues, development of drug resistance, and even environmental pollution
The structure of p-NPA was shown in Supplementary Fig. S3) and the hydrolysis was spectrophotometarically monitored at 400 nm
Pig liver esterases (PLEs) belong to mammal carboxylesterase, despite extensive use in organic chemistry synthesis due to their high stereoselectivity and hydrolytic activity[22,26,34,35], little is known about their pharmacological roles, in veterinary medicine
Summary
The widespread use of antibiotic supplements in farm animals is a major contributing factor to drug residues, development of drug resistance, and even environmental pollution. Carboxylesterases (CEs, E.C.3.1.1.1) constitute a major class of hydrolases with high catalytic efficiency. These enzymes are known to hydrolyze such chemical bonds as carboxylic esters and amides. In this study, we cloned and expressed two PLEs: PLE1, PLE6, and the recombinant carboxylesterases were tested for the hydrolysis of AMO and AMP. Both PLE1 and PLE6 efficiently hydrolyzed AMO and AMP, and decreased their antibacterial activities. This is the first study to quantify the hydrolytic activities of pure PLEs towards commonly used veterinary drugs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
