Abstract
Objective: The aim of the present study was to explore the potential biological role of Rv2629 in Mycobacterium smegmatis and Mycobacterium tuberculosis.Methods: Recombinant wild type and mutant Rv2629 strains were constructed. Rv2629 expression was evaluated by real-time PCR and western blot. Microarray and interaction network analyses were used to identify the gene interactions associated with wild type and mutant Rv2629. Bacterial growth was assessed in Balb/c mice infected with wild type and mutant Rv2629 strains using CFU assay and histological analysis of the organs.Results: Overexpression of Rv2629 could delay the entry of the Mycobacterium tuberculosis cells into the log-phase, while Rv2629 decreased the number of ribosomes and the expression of uridylate kinase in Mycobacterium smegmatis. The Gene Ontology (GO) and pathway analysis indicated that 122 genes correlated with wild type Rv2629, whereas the Rv2629 mutation led to decrease in the ribosome production, oxidative phosphorylation, and virulence in Mycobacterium tuberculosis. Overexpression of Rv2629 slightly enhanced the drug resistance of Mycobacterium smegmatis to antibiotics, and increased its survival and pathogenicity in Balb/c mice.Conclusion: It is suggested that Rv2629 is involved in the survival of the clinical drug-resistant strain via bacterial growth repression and bacterial persistence induction.
Highlights
Mycobacterium tuberculosis (M. tuberculosis) infection is the major cause of TB
Previous studies have demonstrated an increase in the expression of Rv2629 at the transcriptional and/or translational levels induced by hypoxia and nitric oxide in clinical isolates of M. tuberculosis (Voskuil et al, 2003; Kassa et al, 2012; Zhang et al, 2014)
It was observed that the average transcriptional level of Rv2629 in clinical isolates during the logarithmic phase was approximately two-fold lower than that noted in M. tuberculosis H37Rv, while during the stationary phase, this level was higher in the clinical isolates than in the control strain
Summary
Mycobacterium tuberculosis (M. tuberculosis) infection is the major cause of TB. In 2016, 9287 new TB cases were reported in the United States and the successful elimination of TB in the United States is not expected to be achieved during this century (Doosti-Irani et al, 2016). The successful survival and evolution of M. tuberculosis is attributed to a large extent to its ability to persist for long periods within the human body in a latent and/or dormant state (Peddireddy et al, 2017). The non-replicating persistent form of M. tuberculosis aids the escape of the pathogen from the host defense mechanisms and provides additional advantage to the bacilli as regards the effect of standard antiTB drugs. This process results in the long term survival of the bacteria for several decades (Voskuil et al, 2003; Keshari et al, 2017)
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