ABSTRACT
@#A two-dimensional preparative liquid chromatographic method was developed for purification of constituents from water extract of Armillaria luteo-virens using reversed phase preparative liquid chromatography(RPLC)coupled with hydrophilic interaction liquid chromatography(HILIC). Seven compounds were isolated from fruit bodies of Armillaria luteo-virens, and their structures were identified on the basis of physicochemical and spectroscopic analyses. These compounds were identified as pyroglutamic acid(1), uridine(2), 2′-deoxyuridine(3), uracil(4), guanosine(5), inosine(6), and adenosine(7). All the compounds were purified and identified from fruit bodies of Armillaria luteo-virens for the first time.
ABSTRACT
Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.