한빛사논문
- 조회910
Sun Young Kim1, Donggyu Kim2,3, Sojin Kim2, Daeun Lee2, Seok‐Jun Mun1,3, Euni Cho1,3, Wooic Son2,3, Kiseok Jang4 and Chul‐Su Yang*,2,3
1Department of Bionano Technology, Hanyang University, Seoul, South Korea
2Department of Molecular and Life Science, Hanyang University, Ansan, South Korea
3Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, South Korea
4Department of Pathology, Hanyang University College of Medicine, Seoul, South Korea
*Corresponding author.
Abstract
The Rv2626c protein of Mycobacterium tuberculosis is a promising vaccine candidate owing to its strong serum antibody response in patients with tuberculosis. However, there is limited information regarding the intracellular response induced by Rv2626c in macrophages. In this study, we demonstrated that Rv2626c interacts with the RING domain of TRAF6 and inhibits lysine (K) 63‐linked polyubiquitination of TRAF6 (E3 ubiquitin ligase activity); this results in the suppression of TLR4 inflammatory signaling in macrophages. Furthermore, we showed that the C‐terminal 123–131‐amino acid Rv2626c motif promotes macrophage recruitment, phagocytosis, M2 macrophage polarization, and subsequent bacterial clearance. We developed rRv2626c‐CA, a conjugated peptide containing the C‐terminal 123–131‐amino acid Rv2626c that targets macrophages, penetrates the cell membrane, and has demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture‐induced sepsis. This multifunctional rRv2626c‐CA has considerably improved potency, with an IC50 that is 250‐fold (in vitro) or 1,000‐fold (in vivo) lower than that of rRv2626c‐WT. We provide evidence for new peptide‐based drugs with anti‐inflammatory and antibacterial properties for the treatment of sepsis.
논문정보
- Research article
- 2020년 12월 (BRIC 등록일 2020-12-11)
- 국내 연구진
- 생명과학 > 감염생물학
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