Tuberculosis (TB), a bacterial infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is a significant
global public health problem. Mycobacterium tuberculosis expresses a unique family of PE_PGRS proteins that have been
implicated in pathogenesis. Despite numerous studies, the functions of most PE_PGRS proteins in the pathogenesis of
mycobacterium infections remain unclear. PE_PGRS45 (Rv2615c) is only found in pathogenic mycobacteria. In this study,
we successfully constructed a recombinant Mycobacterium smegmatis (M. smegmatis) strain which heterologously expresses
the PE_PGRS45 protein. We found that overexpression of this cell wall-associated protein enhanced bacterial viability under
stress in vitro and cell survival in macrophages. MS_PE_PGRS45 decreased the secretion of pro-inflammatory cytokines such
as IL-1β, IL-6, IL-12p40, and TNF-α. We also found that MS_PE_PGRS45 increased the expression of the anti-inflammatory
cytokine IL-10 and altered macrophage-mediated immune responses. Furthermore, PE_PGRS45 enhanced the survival rate
of M. smegmatis in macrophages by inhibiting cell apoptosis. Collectively, our findings show that PE_PGRS45 is a virulent
factor actively involved in the interaction with the host macrophage.
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