Rv2629 Overexpression Delays Mycobacterium smegmatis and Mycobacteria tuberculosis Entry into Log-Phase and Increases Pathogenicity of Mycobacterium smegmatis in Mice

Abstract

<b>Objective:</b> The aim of the present study was to explore the potential biological role of Rv2629 in <i>Mycobacterium smegmatis</i> and <i>Mycobacterium tuberculosis.</i><b>Methods:</b> Recombinant wild type and mutant <i>Rv2629</i> strains were constructed. <i>Rv2629</i> 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 <i>Rv2629</i>. Bacterial growth was assessed in Balb/c mice infected with wild type and mutant <i>Rv2629</i> strains using CFU assay and histological analysis of the organs. <b>Results:</b> Overexpression of <i>Rv2629</i> could delay the entry of the <i>Mycobacterium tuberculosis</i> cells into the log-phase, while <i>Rv2629</i> decreased the number of ribosomes and the expression of uridylate kinase in <i>Mycobacterium smegmatis</i>. The Gene Ontology (GO) and pathway analysis indicated that 122 genes correlated with wild type <i>Rv2629</i>, whereas the <i>Rv2629</i> mutation led to decrease in the ribosome production, oxidative phosphorylation, and virulence in <i>Mycobacterium tuberculosis</i>. Overexpression of <i>Rv2629</i> slightly enhanced the drug resistance of <i>Mycobacterium smegmatis</i> to antibiotics, and increased its survival and pathogenicity in Balb/c mice. <b>Conclusion:</b> It is suggested that <i>Rv2629</i> is involved in the survival of the clinical drug-resistant strain via bacterial growth repression and bacterial persistence induction.