Rv3737 Is Required for Mycobacterium Tuberculosis Growth in Vitro and in Vivo and Correlates With Bacterial Load and Disease Severity in Human Tuberculosis
Abstract Arms:Rv3737 is the sole homologueof multifunctionaltransporter ThrEin Mycobacterium tuberculosis(Mtb). In this study, we aimed to investigate whether this transporter participates in vitroand in vivosurvival 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 survivalusing acell model of infection. In addition, the comparative analysis was conducted to determine the association between Rv3737mRNA expression and disease severity in active pulmonary TB patients. Results:The H37RvΔRv3737 strain exhibited significantlyslow growth rate compared to H37Rv-WT strain in standard culture medium. Additionally, the survival rate of H37Rv-WTstrain in macrophages was 2 folds higher than that of H37RvΔRv3737 at 72 h. A significantlyhigher level of TNF-αand IL-6mRNA expression was observed in macrophages infected with H37RvΔRv3737 as compared to H37Rv-WT. Of note, Rv3737 expression was significantly increased in clinical Mtbisolates than H37Rv-WT. The relative expression level of Rv3737 was positively correlated with lung cavity numberof 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 indemonstrate that the transporter Rv3737 is required for in vitrogrowth and survival of bacteria inside macrophages. In addition, the expression level of Rv3737 is associated with bacterial load and disease severity inpulmonary tuberculosis patients.