Tuberculosis Division of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Huichuan District, Zunyi City, 563000, Guizhou Province, China.
Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Area 2, Yard 9, Beiguan Street, Yongzhun Town, Tongzhou District, Beijing, 101100, China.
BMC Infect Dis. 2022 Mar 14;22(1):256. doi: 10.1186/s12879-021-06967-y.
Rv3737 is the sole homologue of multifunctional transporter ThrE in Mycobacterium tuberculosis (Mtb). In this study, we aimed to investigate whether this transporter participates in vitro and in vivo survival of Mtb.
To characterize the role of Rv3737, we constructed and characterized a Mtb H37RvΔRv3737. This strain was evaluated for altered growth rate and macrophage survival using a cell model of infection. In addition, the comparative analysis was conducted to determine the association between Rv3737 mRNA expression and disease severity in active pulmonary TB patients.
The H37RvΔRv3737 strain exhibited significantly slow growth rate compared to H37Rv-WT strain in standard culture medium. Additionally, the survival rate of H37Rv-WT strain in macrophages was 2 folds higher than that of H37RvΔRv3737 at 72 h. A significantly higher level of TNF-α and IL-6 mRNA expression was observed in macrophages infected with H37RvΔRv3737 as compared to H37Rv-WT. Of note, Rv3737 expression was significantly increased in clinical Mtb isolates than H37Rv-WT. The relative expression level of Rv3737 was positively correlated with lung cavity number of TB patients. Similarly, the higher Rv3737 mRNA level resulted in lower C(t) value by Xpert MTB/RIF assay, demonstrating that a positive correlation between Rv3737 expression and bacterial load in TB patients.
Our data takes the lead in demonstrate that the threonine transporter Rv3737 is required for in vitro growth and survival of bacteria inside macrophages. In addition, the expression level of Rv3737 may be associated with bacterial load and disease severity in pulmonary tuberculosis patients.
Rv3737 是结核分枝杆菌（Mtb）多功能转运蛋白 ThrE 的唯一同源物。在本研究中，我们旨在研究该转运蛋白是否参与 Mtb 的体外和体内存活。
为了表征 Rv3737 的作用，我们构建并表征了 Mtb H37RvΔRv3737。使用感染的细胞模型评估该菌株的生长速率和巨噬细胞存活的变化。此外，进行了比较分析以确定 Rv3737 mRNA 表达与活动性肺结核患者疾病严重程度之间的关联。
与 H37Rv-WT 菌株相比，H37RvΔRv3737 菌株在标准培养基中的生长速度明显较慢。此外，在 72 小时时，H37Rv-WT 菌株在巨噬细胞中的存活率比 H37RvΔRv3737 菌株高 2 倍。与 H37Rv-WT 相比，感染 H37RvΔRv3737 的巨噬细胞中 TNF-α 和 IL-6 mRNA 表达水平明显更高。值得注意的是，临床 Mtb 分离株中的 Rv3737 表达水平明显高于 H37Rv-WT。Rv3737 的相对表达水平与 TB 患者的肺空洞数量呈正相关。同样，Xpert MTB/RIF 检测的 Rv3737 mRNA 水平越高，C(t) 值越低，表明 Rv3737 表达与 TB 患者的细菌负荷之间存在正相关。
我们的数据首次表明，苏氨酸转运蛋白 Rv3737 是细菌在体外生长和在巨噬细胞内存活所必需的。此外，Rv3737 的表达水平可能与肺结核患者的细菌负荷和疾病严重程度有关。
