Plasmodium berghei PIMMS2 promotes ookinete invasion of the Anopheles gambiae mosquito midgut

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Title: Plasmodium berghei PIMMS2 promotes ookinete invasion of the Anopheles gambiae mosquito midgut
Author(s): Ukegbu, CV
Akinosoglou, KA
Christophides, GKC
Vlachou, D
Item Type: Journal Article
Abstract: Mosquito midgut stages of the malaria parasite present an attractive biological system to study host-parasite interactions and develop interventions to block disease transmission. Mosquito infection ensues upon oocyst development that follows ookinete invasion and traversal of the mosquito midgut epithelium. Here, we report the characterization of PIMMS2 (Plasmodium Invasion of Mosquito Midgut Screen candidate 2), a Plasmodium berghei protein with structural similarities to subtilisin-like proteins. PIMMS2 orthologs are present in the genomes of all plasmodia and are mapped between the subtilisin-encoding genes SUB1 and SUB3. P. berghei PIMMS2 is specifically expressed in zygotes and ookinetes and is localized on the ookinete surface. Loss of PIMMS2 function through gene disruption by homologous recombination leads to normal development of motile ookinetes that exhibit severely impaired capacity to traverse the mosquito midgut and transform to oocysts. Genetic complementation of the disrupted locus with a mutated PIMMS2 allele reveals that amino acid residues corresponding to the putative subtilisin-like catalytic triad are important but not essential for the protein function. Our data demonstrate that PIMMS2 is a novel ookinete-specific protein that promotes parasite traversal of the mosquito midgut epithelium and establishment of mosquito infection.
Publication Date: 30-May-2017
Date of Acceptance: 11-May-2017
URI: http://hdl.handle.net/10044/1/49283
DOI: https://dx.doi.org/10.1128/IAI.00139-17
ISSN: 1098-5522
Publisher: American Society for Microbiology
Journal / Book Title: Infection and Immunity
Volume: 85
Issue: 8
Sponsor/Funder: Commission of the European Communities
Wellcome Trust
Wellcome Trust
Wellcome Trust
Funder's Grant Number: 223736
093587/Z/10/Z
107983/Z/15/Z
107983/Z/15/Z Wellcome Trust
Copyright Statement: © 2017 Ukegbu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/)
Keywords: 06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Microbiology
Publication Status: Published
Article Number: e00139-17
Appears in Collections:Faculty of Natural Sciences



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