Distribution of Tuberculosis Drug Resistance Genes in Patients with Hepatitis B Complicated with Mycobacterium Tuberculosis Infection
Objective:To examine the M.tuberculosis strain diversity and describe the frequency and molecular mechanisms of resistance against first-line TB drugs in TB/HBV co-infected patients.Methods:A total of 100 strains of Mycobacterium tuberculosis from TB/HBV co-infected patients were analyzed retrospec-tively,among which Beijing strain was the most common(49%),followed by EAI strain(35%),and a few strains included Haarlem(2.0%),LAM(1.0%),MANU(3.0%)and T(4.0%).All strains were isolated from sputum and pleural effusion samples of patients from 2014 to 2018.Drug susceptibility testing,spoligoty-ping and 24-locus Mycobacterial Interspersed Repetitive Unit(MIRU-24 typing)were performed,and the rpoB,katG,inhA and inhA promoter,rpsL,rrs and embB genes were sequenced in all drug resistant isolates identified.Results:In total,42/100(42.0%)strains showed drug resistance;9(9.0%)were multi-drug resistant(MDR).Resistance rates were 25.0%(25/100)to isoniazid,10.0%(10/100)to rifampicin,5.0%(5/100)to ethambutol,and 40.0%(40/100)to streptomycin.Among rifampicin-resistant strains,90%(9/10)of the isolates with rifampicin resistance had mutations in the RRDR(codons 507-533).A-mong isoniazid-resistant strains,mutations were found in 100%and 21%of katG and inhA(including the inhA promoter),respectively;their multidrug resistance was mainly associated with the Ser315Thr mutation in the katG gene(7/9,77.8%).59.5%of the strains with resistance belonged to the Beijing spectrum,and 66.7%of the MDR strains belonged to the Beijing spectrum.Conclusion:Nearly half(42%)of M.tubercu-losis isolates from TB/HBV co-infected patients are drug-resistant strains,among which Beijing lineage is the main strain.