Abstract

BackgroundInduced by the pathogen Mycobacterium tuberculosis, tuberculosis remains one of the most dangerous infectious diseases in the world. As a special virus, prophage is domesticated by its host and are major contributors to virulence factors for bacterial pathogenicity. The function of prophages and their genes in M. tuberculosis is still unknown.MethodsRv2650c is a prophage gene in M. tuberculosis genome. We constructed recombinant Mycobacterium smegmatis (M. smegmatis) to observe bacteria morphology and analyze the resistance to various adverse environments. Recombinant and control strains were used to infect macrophages, respectively. Furthermore, we performed ELISA experiments of infected macrophages.ResultsRv2650c affected the spread of colonies of M. smegmatis and enhanced the resistance of M. smegmatis to macrophages and various stress agents such as acid, oxidative stress, and surfactant. ELISA experiments revealed that the Rv2650c can inhibit the expression of inflammatory factors TNF-α, IL-10, IL-1β, and IL-6.ConclusionThis study demonstrates that the prophage gene Rv2650c can inhibit the spread of colonies and the expression of inflammatory factors and promote intracellular survival of M. smegmatis. These results build the foundation for the discovery of virulence factors of M. tuberculosis, and provide novel insights into the function of the prophage in Mycobacterium.

Highlights

  • According to the 2020 global tuberculosis (TB) report released by WHO (World Health Organization [WHO], 2020), about 2 billion people were latently infected by Mycobacterium tuberculosis and 1.41 million people had fallen ill with TB in 2019

  • Western blot analysis confirmed that Rv2650c from M. tuberculosis was successfully expressed in M. smegmatis and localized on the cell wall (Figure 1)

  • Because the Rv2650c confers the ability of recombinant bacteria to resist harsh environments, we further studied the intracellular survival of MS_Rv2650c and MS_Vec in macrophages

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Summary

Introduction

According to the 2020 global tuberculosis (TB) report released by WHO (World Health Organization [WHO], 2020), about 2 billion people were latently infected by Mycobacterium tuberculosis and 1.41 million people had fallen ill with TB in 2019. Tuberculosis is still one of the most prevalent and deadly infectious diseases in the world. Most genes encoding virulence factors of M. tuberculosis are present in the genome of Mycobacterium smegmatis (M. smegmatis), whereby such genes from M. smegmatis can replace their homologous genes in M. tuberculosis and cause disease (Cambier et al, 2014). M. smegmatis is a kind of non-pathogenic environmental saprophytic mycobacteria. This raises the question of whether there are any unknown specific virulence factors that play a key and irreplaceable role in the pathogenesis and intracellular survival of M. tuberculosis. Induced by the pathogen Mycobacterium tuberculosis, tuberculosis remains one of the most dangerous infectious diseases in the world. The function of prophages and their genes in M. tuberculosis is still unknown

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