Tuberculosis (TB) is the deadly infectious disease challenging the public health globally and its impact is further aggravated by co-infection with HIV and the emergence of drug resistant strains of Mycobacterium tuberculosis. In this study, we attempted to characterise the Rv2004c encoded protein, a member of DosR regulon, for its role in drug resistance. In silico docking analysis revealed that Rv2004c binds with streptomycin (SM). Phosphotransferase assay demonstrated that Rv2004c possibly mediates SM resistance through the aminoglycoside phosphotransferase activity. Further, E. coli expressing Rv2004c conferred resistance to 100μM of SM in liquid broth cultures indicating a mild aminoglycoside phosphotransferase activity of Rv2004c. Moreover, we investigated the role of MSMEG_3942 (an orthologous gene of Rv2004c) encoded protein in intracellular survival, its effect on in-vitro growth and its expression in different stress conditions by over expressing it in Mycobacterium smegmatis (M. smegmatis). MSMEG_3942 overexpressing recombinant M. smegmatis strains grew faster in acidic medium and also showed higher bacillary counts in infected macrophages when compared to M. smegmatis transformed with vector alone. Our results are likely to contribute to the better understanding of the involvement of Rv2004c in partial drug resistance, intracellular survival and adaptation of bacilli to stress conditions.

结核病（TB）是一种致命的传染病，在全球范围内挑战着公共卫生，而与HIV的共同感染和结核分枝杆菌耐药菌株的出现进一步加剧了其影响。在这项研究中，我们试图表征Rv2004c编码的蛋白（DosR regulon的成员）在抗药性中的作用。在计算机对接分析中发现Rv2004c与链霉素（SM）结合。磷酸转移酶分析表明，Rv2004c可能通过氨基糖苷磷酸转移酶活性介导SM抗性。此外，大肠杆菌表达Rv2004c的人在液体肉汤培养物中赋予对100μMSM的抗性，表明Rv2004c具有轻度的氨基糖苷磷酸转移酶活性。此外，我们调查了MSMEG_3942（Rv2004c的直系同源基因）编码蛋白在细胞内存活中的作用，其对体外生长的影响以及通过在耻垢分枝杆菌（M. smegmatis）中过度表达而在不同胁迫条件下的表达。MSMEG_3942过表达的重组耻垢分枝杆菌菌株在酸性培养基中生长较快，并且与耻垢分枝杆菌相比，在感染的巨噬细胞中也显示出较高的细菌数单独用矢量转换。我们的结果可能有助于更好地了解Rv2004c参与部分耐药性，细胞内存活以及细菌对压力条件的适应性。