Abstract: Objective  To validate the rifampicin (RFP)dependent characteristics of M. tuberculosis clinical isolate in mice, and identify the characteristics of RFPdependent strains.   Methods  RFP-dependent strains were selected from RFP-resistant clinical isolates on 7H11 medium (the final concentrations of rifampicin were 1 μg/ml and 10 μg/ml). The dependence was further studied in mouse TB model, in which the mice were treated with 0.5% carboxymethyl cellulose sodium (control group), 10 mg/kg rifabutin (Rfb₁₀ group), 10 mg/kg RFP (RFP₁₀ group) and 20 mg/kg RFP (RFP₂₀ group), respectively. The differences of rpoB gene mutations between RFP-dependent and non-dependent strains were analyzed.   Results  18 of 46 RFP-resistant isolates were RFP-dependent. After treatment with RFP or Rfb for 8 weeks in mouse model challenged by aerosol with RFP-dependent clinical isolate，the lung CFU counts showed a concentration-dependent increase (RFP₂₀ group lgCFU were 6.60±0.82, RFP₁₀ group 6.44±0.36、Rfb₁₀ group 6.32±0.55、control group 6.20±0.28)，but there were not significant difference in comparasion with control group (F value were 0.68, 2.21, 2.45, P>0.05). Five of 8 RFP-dependent strains and 10 of 11 non-dependent strains had mutations of  rpoB codon 526 and 531, respectively.   Conclusion  RFP-dependent strains did exist and showed a high prevalence, and the dependence was further validated in mouse TB model. The RFPdependent and non-dependent strains had common rpoB mutations, whether the dependence is a result of phenotype variation needs more evidence.

Key words: Mycobacterium tuberculosis, Rifampicin, Bacterial proteins, Mutation