Inhibition of sexual stage-specific proteins results in reduced numbers of sexual stages and oocysts of Cystoisospora suis (Apicomplexa: Coccidia) in vitro

• Published in: International journal for parasitology Vol. 52; no. 13-14; pp. 829 - 841
• Main Authors: Feix, Anna Sophia, Cruz-Bustos, Teresa, Ruttkowski, Bärbel, Joachim, Anja
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2022
• Subjects: Animals; Apicomplexa; Coccidia - physiology; Enkurin; Hapless protein 2; Isospora suis; Life Cycle Stages; Merozoites - metabolism; Oocyst wall protein 1; Oocysts; Sarcocystidae - genetics; Sexual development; Swine; Isospora suis; Enkurin; Apicomplexa; Sexual development; Hapless protein 2; Oocyst wall protein 1
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2022.09.006

[Display omitted] •Blocking sexual stage-specific proteins of Cystoisospora suis prevents continuation of its life cycle.•Inhibition of OWP1 prohibits development of the oocyst wall in C. suis.•Inhibition of HAP2 prohibits the formation of male gametocytes.•Immunolocalization of enkurin is only detectable in asexual stages. Parasites of the order Coccidia (phylum: Alveolata, subphylum: Apicomplexa) have sophisticated life cycles that include a switch from asexual to sexual development, characterised by distinct cell types. During the development of gametes (gamogony), substantial changes occur at the cellular and subcellular levels, leading to cell fusion of micro- and microgametes, and the development of a zygote that forms a protective outer layer for environmental survival as an oocyst, the transmissible stage. Studies on the porcine coccidian Cystoisospora suis already identified changes in transcription profiles during different time points in the parasite’s development and identified proteins with potential roles in the sexual development of this parasite. Here, we focus on three proteins that are possibly involved in the sexual development of C. suis. Enkurin and hapless protein 2 (HAP2) play important roles in signal transduction and gamete fusion during the fertilisation process, and oocyst wall forming protein 1 (OWP1) is a homologue of oocyst wall forming proteins of related parasites. We evaluated their locations in the different life cycle stages of C. suis and their inhibition by specific antibodies in vitro. Immunolocalization detected enkurin in merozoites and sporulated oocysts, HAP2 in merozoites and microgamonts, and OWP2 in merozoites, macrogamonts, oocysts and sporozoites. Up to 100% inhibition of the development of sexual stages and oocyst formation with purified chicken immunoglobulin IgY sera against recombinant enkurin, HAP2, and especially OWP1, were demonstrated. We conclude that the three investigated sexual stage-specific proteins constitute targets for in vivo intervention strategies to interrupt parasite development and transmission to susceptible hosts.