glmm gene knock-out bacterial strain as well as preparation method and application in sieving mycobacterium tuberculosis phosphoglucomutase inhibitors

Abstract

The invention discloses a glmM gene knock-out bacterial strain ML2009 (mycobacterium smegmatis), CGMCC (China General Microbiological Culture Collection Center) 3418, which is constructed by using phosphoglucomutase participating in the biosynthesis of key components in a mycobacterium tuberculosis cell wall. The bacterial strain ML2009 can be used as a cell model for sieving phosphoglucomutase inhibitors with high flux, be used for sieving effective phosphoglucomutase inhibitors from a combined compound library, traditional Chinese medicine and natural products to prepare tuberculosis-resisting medicaments with high medicine effects; and in addition, in the cells of a human body, the synthesis approach of UDP (Uridine Diphosphate)-acetyl glucosamine is different from that of mycobacterium tuberculosis, no phosphoglucomutase exists in the UDP-acetyl glucosamine, therefore, the reaction catalyzed by the mycobacterium tuberculosis phosphoglucomutase does not exist in the cells of the human body so that the tuberculosis-resisting medicaments developed by using the phosphoglucomutase as a target enzyme are harmless to the human body, and the defect that the traditional antibacterial medicament also kill normal cells is overcome.

Description

Technical field: [0001] The invention relates to a strain for screening anti-tuberculosis drugs, in particular to a glmM gene knockout strain, a preparation method, use and a method for screening Mycobacterium tuberculosis phosphoglucosamine mutase inhibitors. Background technique: [0002] Mycobacterium tuberculosis (Mycobacterium tuberculosis) is the pathogen that causes tuberculosis (tuberculosis), according to WHO report [1] At present, nearly one-third of people in the world have been infected with Mycobacterium tuberculosis, and about 90 million new tuberculosis patients occur every year. Due to the emergence of multi-drug resistant (MDR) strains and extensive drug resistant (XDR) strains, some existing first-line and second-line anti-tuberculosis drugs cannot effectively cure tuberculosis [2] , Resulting in about 2 million deaths each year, tuberculosis has become one of the major diseases in the world for adult deaths due to infectious diseases. [0003] At present, new dru...

AI Technical Summary

Problems solved by technology

However, so far, there is no relevant report on screening effective phosphoglucosamine mutase inhibitors from existing combinatorial compound libraries and traditional Chinese medicines using phosphoglucosamine mutase as the target of anti-tuberculosis drugs.