The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation

Jing Wang, Pupu Ge, Lihua Qiang, Feng Tian, Dongdong Zhao, Qiyao Chai, Mingzhao Zhu, Rongbin Zhou, Guangxun Meng, Yoichiro Iwakura, George Fu Gao and Cui Hua Liu ()
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Jing Wang: Chinese Academy of Sciences
Pupu Ge: Chinese Academy of Sciences
Lihua Qiang: Chinese Academy of Sciences
Feng Tian: Peking University
Dongdong Zhao: Chinese Academy of Sciences
Qiyao Chai: Chinese Academy of Sciences
Mingzhao Zhu: Chinese Academy of Sciences
Rongbin Zhou: University of Science and Technology of China
Guangxun Meng: Chinese Academy of Sciences
Yoichiro Iwakura: Tokyo University of Science
George Fu Gao: Chinese Academy of Sciences
Cui Hua Liu: Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-16

Abstract: Abstract Mycobacterium tuberculosis PtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as GADD45A). PtpA can bind directly to the promoter region of GADD45A in vitro. Both phosphatase activity and DNA-binding ability of PtpA are important in suppressing host innate immune responses. Furthermore, PtpA-expressing Mycobacterium bovis BCG promotes proliferation and migration of human lung adenoma A549 cells in vitro and in a mouse xenograft model. Further research is needed to test whether mycobacteria, via PtpA, might affect cell proliferation or migration in humans.

Date: 2017
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DOI: 10.1038/s41467-017-00279-z

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