Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes

Genwei Zhang; Guodong Niu; Diana Hooker–Romera; Sadeq Shabani; Julian Ramelow; Xiaohong Wang; Noah S. Butler; Anthony A. James; Jun Li

doi:10.3389/fcimb.2023.1132647

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Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes

Journal article

Open access

Peer reviewed

Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes

Genwei Zhang, Guodong Niu, Diana Hooker–Romera, Sadeq Shabani, Julian Ramelow, Xiaohong Wang, Noah S. Butler, Anthony A. James and Jun Li

Frontiers in cellular and infection microbiology, Vol.13, 1132647

03/01/2023

DOI: 10.3389/fcimb.2023.1132647

PMCID: PMC10064449

PMID: 37009496

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Abstract

Plasmodium ookinetes use an invasive apparatus to invade mosquito midguts, and tubulins are the major structural proteins of this apical complex. We examined the role of tubulins in malaria transmission to mosquitoes. Our results demonstrate that the rabbit polyclonal antibodies (pAb) against human α-tubulin significantly reduced the number of P. falciparum oocysts in Anopheles gambiae midguts, while rabbit pAb against human β-tubulin did not. Further studies showed that pAb, specifically against P. falciparum α-tubulin-1, also significantly limited P. falciparum transmission to mosquitoes. We also generated mouse monoclonal antibodies (mAb) using recombinant P. falciparum α-tubulin-1. Out of 16 mAb, two mAb, A3 and A16, blocked P. falciparum transmission with EC50 of 12 μg/ml and 2.8 μg/ml. The epitopes of A3 and A16 were determined to be a conformational and linear sequence of EAREDLAALEKDYEE, respectively. To understand the mechanism of the antibody-blocking activity, we studied the accessibility of live ookinete α-tubulin-1 to antibodies and its interaction with mosquito midgut proteins. Immunofluorescent assays showed that pAb could bind to the apical complex of live ookinetes. Moreover, both ELISA and pull-down assays demonstrated that insect cell-expressed mosquito midgut protein, fibrinogen-related protein 1 (FREP1), interacts with P. falciparum α-tubulin-1. Since ookinete invasion is directional, we conclude that the interaction between Anopheles FREP1 protein and Plasmodium α-tubulin-1 anchors and orients the ookinete invasive apparatus towards the midgut PM and promotes the efficient parasite infection in the mosquito.

FREP1

invasive apparatus

malaria transmission-blocking vaccine

mosquito

ookinete

pathogen-host interaction

Details

Title: Subtitle: Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes
Creators: Genwei Zhang - University of Oklahoma
Guodong Niu - University of Miami
Diana Hooker–Romera - University of Miami
Sadeq Shabani - University of Miami
Julian Ramelow - University of Miami
Xiaohong Wang - University of Miami
Noah S. Butler - University of Iowa
Anthony A. James - University of California, Irvine
Jun Li - University of Oklahoma
Resource Type: Journal article
Publication Details: Frontiers in cellular and infection microbiology, Vol.13, 1132647
DOI: 10.3389/fcimb.2023.1132647
PMID: 37009496
PMCID: PMC10064449
NLM abbreviation: Front Cell Infect Microbiol
ISSN: 2235-2988
eISSN: 2235-2988
Publisher: Frontiers Media S.A
Language: English
Date published: 03/01/2023
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984380369202771

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