The Vibrio alginolyticus T3SS effectors, Val1686 and Val1680, induce cell rounding, apoptosis and lysis of fish epithelial cells

ABSTRACT

Vibrio alginolyticus is a Gram-negative bacterium that is an opportunistic pathogen of both marine animals and people. Its pathogenesis likely involves type III secretion system (T3SS) mediated induction of rapid apoptosis, cell rounding and osmotic lysis of infected eukaryotic cells. Herein, we report that effector proteins, Val1686 and Val1680 from V. alginolyticus, were responsible for T3SS-mediated death of fish cells. Val1686 is a Fic-domain containing protein that not only contributed to cell rounding by inhibiting Rho guanosine triphosphatases (GTPases), but was requisite for the induction of apoptosis because the deletion mutant (Δ val1686) was severely weakened in its ability to induce cell rounding and apoptosis in fish cells. In addition, Val1686 alone was sufficient to induce cell rounding and apoptosis as evidenced by the transfection of Val1686 into fish cells. Importantly, the Fic-domain essential for cell rounding activity was equally important to activation of apoptosis of fish cells, indicating that apoptosis is a downstream event of Val1686-dependent GTPase inhibition. V. alginolyticus infection likely activates JNK and ERK pathways with sequential activation of caspases (caspase-8/-10, -9 and -3) and subsequent apoptosis. Val1680 contributed to T3SS-dependent lysis of fish cells in V. alginolyticus, but did not induce autophagy as has been reported for its homologue (VopQ) in V. parahaemolyticus. Together, Val1686 and Val1680 work together to induce apoptosis, cell rounding and cell lysis of V. alginolyticus-infected fish cells. These findings provide new insights into the mechanism of cell death caused by T3SS of V. alginolyticus.

Journal

Journal ID (nlm-ta): Virulence

Journal ID (iso-abbrev): Virulence

Journal ID (publisher-id): KVIR

Journal ID (publisher-id): kvir20

Title: Virulence

Publisher: Taylor & Francis

ISSN (Print): 2150-5594

ISSN (Electronic): 2150-5608

Publication date Collection: 2018

Publication date (Electronic): 27 February 2018

Publication date PMC-release: 27 February 2018

Volume: 9

Issue: 1

Pages: 318-330

Affiliations

[a ]Institute of Marine Biology, College of Oceanography, Hohai University , Nanjing, Jiangsu, PR China

[b ]Key Laboratory of Marine Bio-resources Sustainable Utilization, Key Laboratory of Applied Marine Biology of Guangdong Province, South China Sea Institute of Oceanology, Chinese Academy of Sciences , Guangzhou, Guangdong, PR China

[c ]Paul G. Allen School for Global Animal Health, Washington State University , Pullman, WA, U.S

[d ]Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences , Guangzhou, Guangdong, PR China

Author notes

CONTACT Zhe Zhao, Ph.D. zhezhao@ 123456hhu.edu.cn Institute of Marine Biology, College of Oceanography, Hohai University , No.1 Xikang Road, Nanjing 210098, P.R. China

Supplemental data for this article can be accessed on the publisher's website.

[†]

The authors contributed equally to this work.

Article

Publisher ID: 1414134

DOI: 10.1080/21505594.2017.1414134

PMC ID: 5955196

PubMed ID: 29252102

Copyright statement: © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Page count

Figures: 7, Tables: 0, Equations: 0, References: 58, Pages: 13

Product

Funding

Funded by: National Natural Science Foundation of China (NSFC)

Award ID: 41276163

National Natural Science Foundation of China (NSFC), (41276163);

Categories

Subject: Research Paper