PPE27 in Mycobacterium smegmatis Enhances Mycobacterial Survival and Manipulates Cytokine Secretion in Mouse Macrophages.

Abstract

Mycobacterium tuberculosis PE/PPE family proteins play a vital role in antigenic diversity, host-pathogen interactions, and immune evasion. As secreted by ESX-5 system, M. tuberculosis PPE27 is related to the growth and virulence of the bacilli. In this study, we expressed PPE27 in the nonpathogenic fast growing Mycobacterium smegmatis. We found that the recombinant strain exhibits higher survival rate under several hostile conditions in vitro and longer persistence in mouse tissues. The survival of the recombinant strains was also enhanced in the mouse macrophage ANA-1, accompanied by higher level of host cell death, higher secretion of tumor necrosis factor-alpha, and a slightly higher amount of interleukin (IL)-1β, which could be abolished by the nuclear factor-κB, p38, and ERK inhibitors. In addition, the recombinant strain robustly induced larger amount of nitric oxide (NO) and lower amount of IL-6 after infection of mouse macrophages. In brief, our data suggest that PPE27 promotes the survival of nonpathogenic M. smegmatis in vitro by manipulating the expression of multiple cytokines, NO, and affecting host cell necrosis, which provide a new insight to understand the functions of this gene.