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TKL3 regulates blood-stage fitness, male gamete fertility, and transmission-stage development in Plasmodium berghei.

Created on 09 Sep 2026

Authors

Himadri Shukla, Nirdosh, Satish Mishra

Published in

PLoS pathogens. Volume 22. Issue 9. Pages e1014582. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

Malaria parasites must undergo complex developmental transitions to complete their life cycle and transmit between vertebrate and mosquito hosts. These transitions are tightly regulated by protein phosphorylation events, yet the specific kinases involved remain poorly characterized. Here, we investigate the role of a previously uncharacterized tyrosine kinase-like protein, TKL3, in the rodent malaria parasite Plasmodium berghei. We show that TKL3 is expressed in blood stages, schizonts, gametocytes, zygotes, and ookinetes and localizes to the cytoplasm. Targeted disruption of the TKL3 gene impairs asexual blood-stage growth, male gamete fertility, and consequently compromises ookinete development. Although oocyst numbers are significantly reduced in mosquitoes, the sporozoites that do form are morphologically normal, retain hepatocyte infectivity, and complete liver-stage development. However, TKL3 knockout sporozoites showed delayed blood-stage patency due to reduced asexual replication. These findings identify TKL3 as an important regulator of parasite growth and transmission, providing new insights into kinases involved in the Plasmodium life cycle.

PMID:
42709869
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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