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Extracellular vesicles participate in proteostasis and heat shock adaptation in Plasmodium falciparum

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Heat shock is a hallmark of clinical malaria, where Plasmodium falciparum parasites are exposed to recurrent febrile episodes exceeding 40 °C, which lead to acute proteotoxic stress. Parasite survival under these conditions relies on efficient proteostasis mechanisms and molecular chaperones, yet how stress resilience is coordinated beyond chaperone responses remains poorly understood.

Here, we identify a stress-associated role for extracellular vesicles (EVs) in parasite heat shock adaptation linked to vesicular trafficking mediated by PfVps60, an Endosomal Sorting Complex Required for Transport (ESCRT) protein. Using a PfVps60 knockout (PfVps60KO) line, we show that disruption of ESCRT-dependent vesicular trafficking affects EV cargo composition during thermal stress. Proteomic profiling revealed that 44.8% of EV-associated proteins from P. falciparum 3D7 overlapped with a previously defined set of aggregation-prone proteins. Loss of PfVps60 impaired EV-mediated export of the chaperones PfHsp70-x and PfHsp110, altered aggregation dynamics and induced the redistribution of protein aggregates near the parasitophorous vacuole, reduced induction of the cytosolic chaperone PfHsp70-1, and resulted in early loss of parasite viability following heat shock.  

Supplementation of PfVps60KO parasites with EVs derived from heat-stressed 3D7 parasites partially rescued heat shock tolerance in a dosedependent manner. EVs released shortly after thermal stress were enriched in aggregation-prone proteins and associated with neighbouring uninfected erythrocytes, suggesting EV-mediated intercellular communication during febrile episodes. Together, these findings support a role for EV-associated cargo as a previously unexplored component of  P. falciparum proteostasis during heat shock adaptation, identifying stress-induced EVs as a potential parasite vulnerability for malaria intervention.

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Emerging Microbes & Infections, 2026, vol. 15, num.1

# metadata.dc.rights[].value
cc-by (c)  Avalos-Padilla, Y. et al., 2026

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

# metadata.dc.title[].value
Extracellular vesicles participate in proteostasis and heat shock adaptation in Plasmodium falciparum