MicroRNA-27a Controls the Intracellular Survival of Mycobacterium Tuberculosis by Regulating Calcium-associated Autophagy

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Oct 18

PMID 30327467

Citations 64

Authors

Feng Liu

Jianxia Chen

Peng Wang

Haohao Li

Yilong Zhou

Haipeng Liu

Zhonghua Liu

Ruijuan Zheng

Lin Wang

Hua Yang

Zhenling Cui

Fei Wang

Xiaochen Huang

Jie Wang

Wei Sha

Heping Xiao

Baoxue Ge

Affiliations

Soon will be listed here.

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.

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