Evolutionary insights into the microneme-secreted, chitinase-containing high molecular weight protein complexes involved in Plasmodium invasion of the mosquito midgut.

While general mechanisms by which Plasmodium ookinetes invade the mosquito midgut have been studied, details remain to be understood regarding the interface of the ookinete, specifically its barriers to invasion, such as the proteolytic milieu, the chitin-containing, protein cross-linked peritrophic matrix, and the midgut epithelium. Here we review knowledge of Plasmodium chitinases and the mechanisms by which they mediate the ookinete crossing the peritrophic matrix. The integration of new genomic insights into previous findings advances our understanding of Plasmodium evolution. Recently obtained Plasmodium spp. genomic data enable identification of the conserved residues in the experimentally demonstrated hetero-multimeric, high molecular weight complex comprised of a short chitinase covalently linked to binding partners, von Willebrand factor A domain-related protein (WARP) and secreted ookinete adhesive protein (SOAP). Artificial intelligence-based high-resolution structural modeling using the DeepMind AlphaFold algorithm yielded highly informative 3D structures and insights into how short chitinases, WARP, and SOAP may interact at the atomic level to form the ookinete-secreted peritrophic matrix invasion complex. Elucidating the significance of the divergence of ookinete-secreted micronemal proteins among Plasmodium species could lead to a better understanding of ookinete invasion machinery and the co-evolution of Plasmodium-mosquito interactions.