Rv3737 is required for Mycobacterium tuberculosis growth in vitro and in vivo and correlates with bacterial load and disease severity in human tuberculosis.
Rv3737 is required for Mycobacterium tuberculosis growth in vitro and in vivo and correlates with bacterial load and disease severity in human tuberculosis.
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DOI：
10.1186/s12879-021-06967-y
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发表时间：
2022-03-14
影响因子：
3.7
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Li Q;Peng Z;Fu X;Wang H;Zhao Z;Pang Y;Chen L
Rv3737 是结核分枝杆菌 (Mtb) 中多功能转运蛋白 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结核分枝杆菌的体外和体内存活。为了表征 Rv3737 的作用，我们构建并表征了 Mtb H37RvΔRv3737。使用感染细胞模型评估该菌株的生长速率和巨噬细胞存活率的变化。此外，还进行了比较分析以确定活动性肺结核患者中 Rv3737 mRNA 表达与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表现出显着缓慢的生长速率。此外，H37Rv-WT菌株在巨噬细胞中的存活率在72小时时比H37RvΔRv3737高2倍。与 H37Rv-WT 相比，在感染 H37RvΔRv3737 的巨噬细胞中观察到 TNF-α 和 IL-6 mRNA 表达水平显着更高。值得注意的是，与 H37Rv-WT 相比，临床 Mtb 分离株中的 Rv3737 表达显着增加。 Rv3737的相对表达水平与结核病患者肺腔数呈正相关。同样，通过 Xpert MTB/RIF 测定，较高的 Rv3737 mRNA 水平导致较低的 C(t) 值，表明结核病患者中 Rv3737 表达与细菌负荷之间呈正相关。我们的数据率先证明苏氨酸转运蛋白 Rv3737 是巨噬细胞内细菌的体外生长和存活所必需的。此外，Rv3737的表达水平可能与肺结核患者的细菌载量和疾病严重程度相关。在线版本包含可在 10.1186/s12879-021-06967-y 获取的补充材料。
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. The online version contains supplementary material available at 10.1186/s12879-021-06967-y.
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DOI：
10.1016/j.ijbiomac.2020.03.037
发表时间：
2020-06-15
影响因子：
8.2
作者：
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通讯作者：
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影响因子：
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影响因子：
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
3.7
作者：
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