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Background 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 . Methods 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. Results 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. Conclusions 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.

bmc infectious diseases

Rv3737 is required for Mycobacterium tuberculosis growth in vitro and in vivo and correlates with bacterial load and disease severity in human tuberculosis