Mycobacterium tuberculosis RKIP (Rv2140c) dephosphorylates ERK/NF- κB upstream signaling molecules to subvert macrophage innate immune response

In this report, we show that Rv2140c can mimic the mammalian RKIP function. Rv2140c inhibit the activation of extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) via decreasing the phosphorylation capacity of upstream mediators MEK1, ERK1/2, and IKKα/β, thus leading to a reduction in pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. This effect can be reversed by RKIP inhibitor locostatin. Furthermore Rv2140c mediates apoptosis associated with activation of caspases cascades. This modulation enhances the intracellular survival of M. smegmatis within macrophage. We propose that Rv2140c is a multifunctional virulence factor and a promising novel anti-Tuberculosis drug target.PMID:34333158 | DOI:10.1016/j.meegid.2021.105019

Source: Infection, Genetics and Evolution - August 1, 2021 Category: Genetics & Stem Cells Authors: M A Abo-Kadoum Mohammed Assad Moure Uae Stech A E Nzaou Zhen Gong Asmaa Moaaz Samson Teweldebrhan Adel Eltoukhy Ai Xuefeng Yu Chen Jianping Xie Source Type: research