Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum

Yuchen Wang; Yuting Tang; Chen Lin; Junli Zhang; Juntao Mai; Jun Jiang; Xiaoxiao Gao; Yao Li; Guoping Zhao; Lu Zhang; Jun Liu

doi:10.1016/j.isci.2021.103585

Crosstalk between the ancestral type VII secretion system ESX-4 and other T7SS in Mycobacterium marinum

iScience. 2021 Dec 8;25(1):103585. doi: 10.1016/j.isci.2021.103585. eCollection 2022 Jan 21.

Authors

Yuchen Wang^{1

2}, Yuting Tang³, Chen Lin³, Junli Zhang³, Juntao Mai⁴, Jun Jiang³, Xiaoxiao Gao³, Yao Li³, Guoping Zhao¹, Lu Zhang^{1

3

5}, Jun Liu⁴

Affiliations

¹ Department of Microbiology, School of Life Science, Fudan University, Shanghai 200090, China.
² Guizhou institute of Biotechnology, Guiyang 550025, Guizhou, China.
³ State Key Laboratory of Genetic Engineering, School of Life Science, Institute of Genetics, Fudan University, Shanghai 200090, China.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON M5G1M1, Canada.
⁵ Shanghai Engineering Research Center of Industrial Microorganisms, Shanghai 200090, China.

Abstract

The type VII secretion system (T7SS) of Mycobacterium tuberculosis secretes three substrate classes: Esx, Esp, and PE/PPE proteins, that play important roles in bacterial physiology and host interaction. Five subtypes of T7SS, namely ESX-1 to ESX-5, are present in M. tb. ESX-4 is the progenitor of T7SS but its function is not understood. We investigated the ESX-4 system in Mycobacterium marinum. We show that ESX-4 of M. marinum does not secrete its cognate substrates, EsxT and EsxU, under the conditions tested. Paradoxically, the deletion of eccC4, an essential component of ESX-4, resulted in elevated secretion of protein substrates of ESX-1 and ESX-5. Consequently, the ΔeccC4 mutant was more efficient in inducing actin cytoskeleton rearrangement, which led to enhanced phagocytosis by macrophages. Our results reveal an intimate crosstalk between the progenitor of T7SS and its more recent duplication and expansion, and provide new insight into the evolution of T7SS in mycobacteria.

Keywords: Microbiology; Molecular biology.