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Micronemal protein 13 contributes to the optimal growth of Toxoplasma gondii under stress conditions

  • Protozoology - Original Paper
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Abstract

Toxoplasma gondii is a ubiquitous parasitic protozoan infecting humans and a wide variety of animals. Fast-replicating tachyzoites during acute infection and slowly growing bradyzoites during chronic infection are the two basic forms of T. gondii in intermediate hosts. Interconversion between the two contributes to the transmission and pathogenesis of this parasite. Secretory micronemal proteins are thought to mediate interactions with host cells and facilitate parasite invasion, therefore the majority of them are highly expressed in tachyzoites. Micronemal protein 13 (MIC13) is unique in that its expression is low in tachyzoites and is upregulated under bradyzoite-inducing conditions. Previous attempts to disrupt this gene were not successful, implying that it may play critical roles during parasite growth. However, in this study, MIC13 was successfully disrupted in type 1 strain RH and type 2 strain ME49 using CRISPR/Cas9-mediated gene disruption techniques. Consistent with its low expression in tachyzoites and increased expression under stress or bradyzoite-inducing conditions, MIC13-inactivated mutants displayed normal growth, host cell invasion, intracellular replication, and egress, as well as acute virulence at the tachyzoite stage. However, under stress conditions, such as high pH or oxygen limitation, MIC13-disrupted parasites showed significantly slower growth rates compared to the parental strains, suggesting that it is required for optimal parasite growth under bradyzoite-inducing or stress conditions. This is the first micronemal protein reported to have such expression pattern and function modes, which expands our understanding of the diverse functions of micronemal proteins.

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Funding

This work was supported the National Key Research and Development Program of China (Grant no. 2017YFD0500402), the National Basic Science Research Program (973 program) of China (Grant no. 2015CB150300), and the Natural Science Foundation of Hubei Province (Project 2017CFA020). The funders had no role in the study design, data collection and analysis, preparation of the manuscript, or decision to submit the work for publication.

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Authors and Affiliations

  1. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei Province, People’s Republic of China

    Shu Ye, Ningbo Xia, Pengfei Zhao, Jichao Yang, Yanqin Zhou, Bang Shen & Junlong Zhao

  2. Key Laboratory of Preventive Medicine in Hubei Province, Wuhan, Hubei Province, People’s Republic of China

    Bang Shen & Junlong Zhao

  3. Hubei Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei Province, People’s Republic of China

    Junlong Zhao

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  1. Shu Ye
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  2. Ningbo Xia
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  3. Pengfei Zhao
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  4. Jichao Yang
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  5. Yanqin Zhou
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  6. Bang Shen
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Correspondence to Bang Shen or Junlong Zhao.

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All animal experiments were approved by the Ethical Committee of Huazhong Agricultural University (permit no. HZAUMO-2017-023).

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Ye, S., Xia, N., Zhao, P. et al. Micronemal protein 13 contributes to the optimal growth of Toxoplasma gondii under stress conditions. Parasitol Res 118, 935–944 (2019). https://doi.org/10.1007/s00436-018-06197-3

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  • DOI: https://doi.org/10.1007/s00436-018-06197-3

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