Recurrent Fever Promotes Plasmodium falciparum Development in Human Erythrocytes

Soundara Raghavan Pavithra; Gowrishankar Banumathy; Omana Joy; Varslia Singh; Utpal Tatu

doi:10.1074/jbc.M409165200

Recurrent Fever Promotes Plasmodium falciparum Development in Human Erythrocytes

Soundara Raghavan Pavithra
, Gowrishankar Banumathy
, Omana Joy
, Varslia Singh
, Utpal Tatu (Lead / Corresponding author)

Molecular Microbiology

Research output: Contribution to journal › Article › peer-review

80 Citations (Scopus)

86 Downloads (Pure)

Abstract

The human malarial parasite Plasmodium falciparum (Pf) is exposed to wide temperature fluctuations during its life cycle, ranging from 25°C in the mosquito vector and 37°C in humans to 41°C during febrile episodes in the patient. The repeated occurrence of fever at regular intervals is a characteristic of human malaria. We have examined the influence of repeated exposure to elevated temperatures encountered during fever on the intra-erythrocytic development of the parasite. Using flow cytometry, we show that repeated exposure to temperatures mimicking febrile episodes promotes parasite development in human erythrocytes. Heat shock-mediated cytoprotection and growth promotion is dependent on the heat shock protein 90 (PfHsp90) multi-chaperone complex. Inhibition of PfHsp90 function using geldanamycin attenuates temperature-dependent progression from the ring to the trophozoite stage. Geldanamycin inhibits parasite development by disrupting the Pf-Hsp90 complex consisting of PfHsp70, PfPP5, and tubulin, among other proteins. While explaining the contribution of febrile episodes to the pathogenesis of malaria, owr results implicate temperature as an important environmental cue used by the parasite to coordinate its development in humans.

Original language	English
Pages (from-to)	46692-46699
Number of pages	8
Journal	Journal of Biological Chemistry
Volume	279
Issue number	45
DOIs	https://doi.org/10.1074/jbc.M409165200
Publication status	Published - 5 Nov 2004

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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Final published versionFinal published version, 1.17 MBLicence: CC BY

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title = "Recurrent Fever Promotes Plasmodium falciparum Development in Human Erythrocytes",

abstract = "The human malarial parasite Plasmodium falciparum (Pf) is exposed to wide temperature fluctuations during its life cycle, ranging from 25°C in the mosquito vector and 37°C in humans to 41°C during febrile episodes in the patient. The repeated occurrence of fever at regular intervals is a characteristic of human malaria. We have examined the influence of repeated exposure to elevated temperatures encountered during fever on the intra-erythrocytic development of the parasite. Using flow cytometry, we show that repeated exposure to temperatures mimicking febrile episodes promotes parasite development in human erythrocytes. Heat shock-mediated cytoprotection and growth promotion is dependent on the heat shock protein 90 (PfHsp90) multi-chaperone complex. Inhibition of PfHsp90 function using geldanamycin attenuates temperature-dependent progression from the ring to the trophozoite stage. Geldanamycin inhibits parasite development by disrupting the Pf-Hsp90 complex consisting of PfHsp70, PfPP5, and tubulin, among other proteins. While explaining the contribution of febrile episodes to the pathogenesis of malaria, owr results implicate temperature as an important environmental cue used by the parasite to coordinate its development in humans.",

author = "Pavithra, \{Soundara Raghavan\} and Gowrishankar Banumathy and Omana Joy and Varslia Singh and Utpal Tatu",

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T1 - Recurrent Fever Promotes Plasmodium falciparum Development in Human Erythrocytes

AU - Pavithra, Soundara Raghavan

AU - Banumathy, Gowrishankar

AU - Joy, Omana

AU - Singh, Varslia

AU - Tatu, Utpal

PY - 2004/11/5

Y1 - 2004/11/5

N2 - The human malarial parasite Plasmodium falciparum (Pf) is exposed to wide temperature fluctuations during its life cycle, ranging from 25°C in the mosquito vector and 37°C in humans to 41°C during febrile episodes in the patient. The repeated occurrence of fever at regular intervals is a characteristic of human malaria. We have examined the influence of repeated exposure to elevated temperatures encountered during fever on the intra-erythrocytic development of the parasite. Using flow cytometry, we show that repeated exposure to temperatures mimicking febrile episodes promotes parasite development in human erythrocytes. Heat shock-mediated cytoprotection and growth promotion is dependent on the heat shock protein 90 (PfHsp90) multi-chaperone complex. Inhibition of PfHsp90 function using geldanamycin attenuates temperature-dependent progression from the ring to the trophozoite stage. Geldanamycin inhibits parasite development by disrupting the Pf-Hsp90 complex consisting of PfHsp70, PfPP5, and tubulin, among other proteins. While explaining the contribution of febrile episodes to the pathogenesis of malaria, owr results implicate temperature as an important environmental cue used by the parasite to coordinate its development in humans.

AB - The human malarial parasite Plasmodium falciparum (Pf) is exposed to wide temperature fluctuations during its life cycle, ranging from 25°C in the mosquito vector and 37°C in humans to 41°C during febrile episodes in the patient. The repeated occurrence of fever at regular intervals is a characteristic of human malaria. We have examined the influence of repeated exposure to elevated temperatures encountered during fever on the intra-erythrocytic development of the parasite. Using flow cytometry, we show that repeated exposure to temperatures mimicking febrile episodes promotes parasite development in human erythrocytes. Heat shock-mediated cytoprotection and growth promotion is dependent on the heat shock protein 90 (PfHsp90) multi-chaperone complex. Inhibition of PfHsp90 function using geldanamycin attenuates temperature-dependent progression from the ring to the trophozoite stage. Geldanamycin inhibits parasite development by disrupting the Pf-Hsp90 complex consisting of PfHsp70, PfPP5, and tubulin, among other proteins. While explaining the contribution of febrile episodes to the pathogenesis of malaria, owr results implicate temperature as an important environmental cue used by the parasite to coordinate its development in humans.

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DO - 10.1074/jbc.M409165200

M3 - Article

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AN - SCOPUS:8744228200

SN - 0021-9258

VL - 279

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EP - 46699

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 45

ER -

Recurrent Fever Promotes Plasmodium falciparum Development in Human Erythrocytes

Abstract

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