QseC Inhibition as a Novel Antivirulence Strategy for the Prevention of Acute Hepatopancreatic Necrosis Disease (AHPND)-Causing Vibrio parahaemolyticus

Qian Yang; Peizhuo Zou; Zhi Cao; Qingyao Wang; Songzhe Fu; Guosi Xie; Jie Huang

doi:10.3389/fcimb.2020.594652

QseC Inhibition as a Novel Antivirulence Strategy for the Prevention of Acute Hepatopancreatic Necrosis Disease (AHPND)-Causing Vibrio parahaemolyticus

Front Cell Infect Microbiol. 2021 Jan 21:10:594652. doi: 10.3389/fcimb.2020.594652. eCollection 2020.

Authors

Qian Yang^{1

2

3

4}, Peizhuo Zou^{1

2

3}, Zhi Cao^{1

2

3}, Qingyao Wang^{5

6}, Songzhe Fu^{5

6}, Guosi Xie^{1

2

3}, Jie Huang^{1

2

3

7}

Affiliations

¹ Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
² Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture and Rural Affairs, Qingdao, China.
³ Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China.
⁴ Center for Microbial Ecology and Technology (CMET), Ghent University, Gent, Belgium.
⁵ College of Marine Science and Environment, Dalian Ocean University, Dalian, China.
⁶ Key Laboratory of Environment Controlled Aquaculture (KLECA), Ministry of Education, Dalian, China.
⁷ Network of Aquaculture Centers in Asia-Pacific, Bangkok, Thailand.

Abstract

Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus resulted in great economic losses in global shrimp aquaculture. There is an urgent need for development of novel strategies to combat AHPND-causing V. parahaemolyticus (Vp_AHPND), given that one of the greatest challenges currently is the widespread use of antibiotics and subsequent emergence of multidrug-resistant bacteria. Here, we proposed a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, which has been demonstrated to activate virulence expression in several Gram-negative pathogens. Our results showed that QseC mediated the catecholamine stimulated effects on growth and flagellar motility of Vp_AHPND. Transcriptome analysis revealed that QseC was involved in the global regulation of the virulence of Vp_AHPND as the ΔqseC mutant exhibited a decreased expression of genes related to type IV pilin, flagellar motility, and biofilm formation, while an overexpression of type VI secretion system and cell wall biosynthesis. Subsequently, the bacterial catecholamine receptor antagonist LED209 not only neutralized the stimulatory effects of host catecholamines on the growth and motility of Vp_AHPNDin vitro, but also attenuated the virulence of Vp_AHPND towards brine shrimp larvae and white shrimp in vivo. Additionally, LED209 presented no interference with pathogen growth, nor the toxicity to the experimental animals. These results suggest that QseC can be an attractive antivirulence therapy target, and LED209 is a promising candidate for development of broad-spectrum antivirulence agents. This is the first study that demonstrated the role of QseC in the global regulation of Vp_AHPND infection and demonstrated the antivirulence potential of LED209, which provides insight into the use of an antivirulence approach for targeting not only Vp_AHPND, but also a much larger collection of pathogenic bacteria.

Keywords: LED209; QseC; Vibrio parahaemolyticus; acute hepatopancreatic necrosis disease; antivirulence therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aquaculture
Necrosis
Penaeidae*
Type VI Secretion Systems* / genetics
Vibrio parahaemolyticus*

Substances

Type VI Secretion Systems