The QS regulator AphBvp promotes expression of the AHPND PirAvp and PirBvp toxins and may enhance virulence under acidic conditions

Shin-Jen Lin; Phuoc Thien Le; Yuan-Chih Chang; Chang-Yi Liu; Yu-Hsuan Chen; Chao-Jung Wu; Hui-Ju Huang; Kai-Cheng Hsu; Tzu-Ping Ko; Nai-Yueh Tien; Han-Ching Wang; Chu-Fang Lo; Hao-Ching Wang

doi:10.1016/j.ijbiomac.2024.137563

The QS regulator AphB^vp promotes expression of the AHPND PirA^vp and PirB^vp toxins and may enhance virulence under acidic conditions

Int J Biol Macromol. 2024 Nov 15;283(Pt 1):137563. doi: 10.1016/j.ijbiomac.2024.137563. Online ahead of print.

Authors

Shin-Jen Lin¹, Phuoc Thien Le², Yuan-Chih Chang³, Chang-Yi Liu⁴, Yu-Hsuan Chen⁵, Chao-Jung Wu⁶, Hui-Ju Huang⁷, Kai-Cheng Hsu⁸, Tzu-Ping Ko⁹, Nai-Yueh Tien¹⁰, Han-Ching Wang¹¹, Chu-Fang Lo¹², Hao-Ching Wang¹³

Affiliations

¹ International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan, ROC. Electronic address: z10303066@email.ncku.edu.tw.
² International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan, ROC; The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan, ROC; Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, ROC.
³ Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, ROC; Academia Sinica Cryo-EM Center, Academia Sinica, Taipei 115, Taiwan, ROC. Electronic address: kondo@gate.sinica.edu.tw.
⁴ The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan, ROC; Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, ROC.
⁵ The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan, ROC; Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, ROC. Electronic address: itsivy@tmu.edu.tw.
⁶ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, ROC. Electronic address: cjwu813@tmu.edu.tw.
⁷ Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, ROC; Academia Sinica Cryo-EM Center, Academia Sinica, Taipei 115, Taiwan, ROC. Electronic address: huijuhuang@gate.sinica.edu.tw.
⁸ Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, ROC. Electronic address: piki@tmu.edu.tw.
⁹ Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan, ROC. Electronic address: kotping@gate.sinica.edu.tw.
¹⁰ International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan, ROC. Electronic address: z11008084@nuku.edu.tw.
¹¹ International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan, ROC; Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, ROC. Electronic address: wanghc@mail.ncku.edu.tw.
¹² International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan, ROC. Electronic address: gracelow@mail.ncku.edu.tw.
¹³ International Center for the Scientific Development of Shrimp Aquaculture, National Cheng Kung University, Tainan 701, Taiwan, ROC; The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 115, Taiwan, ROC; Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, ROC. Electronic address: wanghc@tmu.edu.tw.

PMID: 39549792
DOI: 10.1016/j.ijbiomac.2024.137563

Abstract

Shrimp acute hepatopancreatic necrosis disease (AHPND) is one of the most devastating diseases to impact the global shrimp farming industry, with a mortality rate of 70 %-100 %. The key virulence factors are a pair of Photorhabdus insect-related (Pir)-like toxins, PirA^vp and PirB^vp. In this study, by using an in vitro transcription and translation assay, we first confirmed that the quorum sensing transcriptional regulator AphB^vp could trigger the expression of its downstream genes after binding to the AphB^vp binding sequence in the promoter region of the pirA^vp/pirB^vp operon. Next, we showed that AphB^vp was essential for the expression of these toxins by using an aphB^vp-deletion mutant (ΔaphB^vp) derived from the AHPND-causing Vibrio parahaemolyticus. Lastly, we discovered that the expression levels of PirA^vp and PirB^vp were up-regulated under acidic conditions (pH 4.5), and further showed that an acidic environment promoted the binding of AphB^vp to the pirAB^vp promoter. We speculate that this was because the acidic environment favored the formation of AphB^vp tetramers, which is important for binding to DNA. Taken together, these findings improve our understanding of the gene regulatory mechanisms of pirA^vp and pirB^vp, and suggest that the pH value of the environment might affect the virulence of AHPND-causing V. parahaemolyticus.

Keywords: AHPND; AphB; PirA; PirB; Quorum sensing; Vibrio parahaemolyticus.