| Bacterial infections are a type of disease that ravages the world,causing diseases and even deaths for millions of people,with direct and indirect economic losses reaching tens of billions of dollars every year.With the emergence of antibiotic-resistant bacteria that have been abused by antibiotics,many antibiotics have lost their original role,causing difficulties in clinical treatment.Therefore,in order to solve this problem,there is an urgent need for new drug and innovation of antibiotics.However,no matter how fast the development of antibiotics is,as long as it is used for a period of time,it will inevitably cause bacterial resistance.Therefore,the development of treatment methods other than antibiotics has become a popular research.The secretion of antibiotic hydrolase is the most common resistance mechanism of bacteria.Among them,the most widely affected are carbopenem antibiotics,metal β-lactamases(MBLs)represented by NDM-1.The emergence of these enzymes makes clinical treatment is almost helpless.Therefore,accelerating the development of treatments for this drug resistance mechanism is an important guarantee related to public health and safety.In recent years,the dual drug combination has been successful in treating some drug-resistant microbial infections.Therefore,this study aims to establish a system for rapid and effective screening of NDM-like β-lactamase inhibitors based on computer virtual screening.In this project,the metal β-lactamase NDM-23 was used as the research object.Through virtual screening,the fluorescent substrate CDC-1was used to construct this system,and 4 Inhibitors were screened.Then at the bacterial level,we used the selected NDM-23 inhibitors in combination with the first-generation β-lactam antibiotics to evaluate the pharmacodynamics of the combination,and narrowed them down to a combination of the Epigallocatechin gallate and cefazolin.It laid the technical and theoretical basis for finding more effective and safer inhibitor clues. |
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