Mutation characteristics of drug resistance genes in multidrug-resistant mycobacterium tuberculosis in Wuhan
	    		
	    			
	    			
		        		
			        		
		        		
			        
		   		
		   		
		   			
		   		
	    	
    	 
    	10.3969/j.issn.1006-2483.2022.06.010
   		
        
        	
        		- VernacularTitle:武汉市耐多药结核分枝杆菌耐药基因突变特征分析
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Jun WU
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Jun CHEN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Mei-lan ZHOU
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Zheng-bin ZHANG
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Tian-tian WANG
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Ai-ping YU
			        		
			        		
			        		
			        			2
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Qiong-hong DUAN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. Wuhan Pulmonary Hospital, Wuhan , Hubei 430030 , China
			        		
			        			2. Wuhan Dongxihu Center for Disease Control and Prevention, Wuhan , Hubei 430040 , China
			        		
		        		
	        		
        		 
        	
        	
        	
        		- Publication Type:Journal Article
 
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Mycobacterium tuberculosis;
			        		
			        		
			        		
				        		Whole-genome sequencing;
			        		
			        		
			        		
				        		Drug-resistance
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Journal of Public Health and Preventive Medicine
	            		
	            		 2022;33(6):42-46
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
            	- 
		        	Abstract:
			       	
			       		
				        
				        	Objective  To investigate the mutation characteristics of drug resistance genes of multidrug-resistant mycobacterium tuberculosis in Wuhan, and to provide evidence for molecular diagnosis of drug-resistant tuberculosis.  Methods  Whole-genome sequencing was performed on 149 isolates collected from Wuhan Pulmonary Hospital in 2017 to obtain the specific mutation of genotype or subtype of H37Rv and the drug-resistant gene mutation of anti-TB drugs. The correlation between major mutation types and genotypes or subtypes was analyzed.  Results  Among the 149 strains, the major mutation types of resistance-related genes to common anti-tuberculosis drugs were katG Ser315Thr (65.77%, isoniazid), ropB Ser450Leu (62.42%, rifampicin), rpsL Lys43Arg (46.31%, streptomycin), embB Met306Val (20.13%, ethambutol), pncA -11 T>C (3.36%, pyrazinamide), gyrA Ala90Val (10.07%, ofloxacin) , rrs -1401 A> G (4.70%, second-line injectable drugs), fabG -15C>T (14.09%, ethionamide), and folC Ile43Thr (3.36%, paza-aminosalicylate). Nine strains of ahpC-OxyR mutation (isoniazid resistance compensatory mutation) and five strains of ropC gene mutation (rifampicin resistance compensatory mutation) were found. The mutation frequency of embB Met306Ile of L4 strain was higher than that of L2, and the mutation frequency of rpsL Lys43Arg was lower than that of L2 (P < 0.05). The difference of mutation frequency of other sites was not statistically significant. The mutation frequency of thyA His75Asn in the ancient subtype was higher than that in the modern type (P<0.05).  Conclusion  The mutation of MDR-TB isolates in Wuhan displays genetic diversity and should be detected by whole genome sequencing rather than targeted molecular approaches, which may miss some mutations. Some mutation types of MDR-related genes are related to the genotype and subtype of the strains.