Inhibition of signal peptidase complex expression affects the development and survival of Schistosoma japonicum

Wen-Bin Yang; Fang Luo; Wei Zhang; Cheng-Song Sun; Cong Tan; An Zhou; Wei Hu

doi:10.3389/fcimb.2023.1136056

Inhibition of signal peptidase complex expression affects the development and survival of Schistosoma japonicum

Front Cell Infect Microbiol. 2023 Mar 3:13:1136056. doi: 10.3389/fcimb.2023.1136056. eCollection 2023.

Authors

Wen-Bin Yang^{1

2

3}, Fang Luo^{1

2}, Wei Zhang^{1

2}, Cheng-Song Sun⁴, Cong Tan^{1

2

3}, An Zhou^{1

2}, Wei Hu^{1

2

3}

Affiliations

¹ State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, Fudan University, Shanghai, China.
² Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China.
³ The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China.
⁴ Central Laboratory, Anhui Provincial Institute of Parasitic Diseases, Anhui, China.

Abstract

Background: Schistosomiasis, the second most neglected tropical disease defined by the WHO, is a significant zoonotic parasitic disease infecting approximately 250 million people globally. This debilitating disease has seriously threatened public health, while only one drug, praziquantel, is used to control it. Because of this, it highlights the significance of identifying more satisfactory target genes for drug development. Protein translocation into the endoplasmic reticulum (ER) is vital to the subsequent localization of secretory and transmembrane proteins. The signal peptidase complex (SPC) is an essential component of the translocation machinery and functions to cleave the signal peptide sequence (SP) of secretory and membrane proteins entering the ER. Inhibiting the expression of SPC can lead to the abolishment or weaker cleavage of the signal peptide, and the accumulation of uncleaved protein in the ER would affect the survival of organisms. Despite the evident importance of SPC, in vivo studies exploring its function have yet to be reported in S. japonicum.

Methods: The S. japonicum SPC consists of four proteins: SPC12, SPC18, SPC22 and SPC25. RNA interference was used to investigate the impact of SPC components on schistosome growth and development in vivo. qPCR and in situ hybridization were applied to localize the SPC25 expression. Mayer's carmalum and Fast Blue B staining were used to observe morphological changes in the reproductive organs of dsRNA-treated worms. The effect of inhibitor treatment on the worm's viability and pairing was also examined in vitro.

Results: Our results showed that RNAi-SPC delayed the worm's normal development and was even lethal for schistosomula in vivo. Among them, the expression of SPC25 was significantly higher in the developmental stages of the reproductive organs in schistosomes. Moreover, SPC25 possessed high expression in the worm tegument, testes of male worms and the ovaries and vitellarium of female worms. The SPC25 knockdown led to the degeneration of reproductive organs, such as the ovaries and vitellarium of female worms. The SPC25 exhaustion also reduced egg production while reducing the pathological damage of the eggs to the host. Additionally, the SPC-related inhibitor AEBSF or suppressing the expression of SPC25 also impacted cultured worms' pairing and viability in vitro.

Conclusions: These data demonstrate that SPC is necessary to maintain the development and reproduction of S. japonicum. This research provides a promising anti-schistosomiasis drug target and discovers a new perspective on preventing worm fecundity and maturation.

Keywords: RNAi; S. japonicum; SPC; SPC25; development; reproduction.

Publication types

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

MeSH terms

Animals
Female
Male
Membrane Proteins / metabolism
Praziquantel
Protein Sorting Signals
Schistosoma japonicum* / genetics

Substances

type I signal peptidase
Membrane Proteins
Praziquantel
Protein Sorting Signals

Grants and funding

This work has been supported by funding from the National Natural Science Foundation of China (grant no. 31725025), Shanghai Municipal Science and Technology Committee of Shanghai outstanding academic leaders plan (grant no. 18XD1400400), Natural Science Foundation of Anhui Province (grant no. 2008085QH430) and Science and Technology Leading Talent Team plan (grant no. 2022SLJRC0023).