Noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites

Agnes Mwakingwe, Li Min Ting, Sarah Hochman, John Chen, Photini Sinnis, Kami Kim

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background: The morbidity and mortality associated with malaria are heightened because of the spread of drug-resistant parasites and the lack of an effective vaccine. Plasmodium liver stages are the targets of new chemotherapeutics and vaccines, but there are limited tools available to study this stage in vivo. Methods: To overcome this obstacle, we developed a method with which to study Plasmodium liver stages by means of bioluminescent imaging (BLI) of the rodent malaria parasite Plasmodium yoelii. We created a P. yoelii YM strain (PyLuc) that stably expresses firefly luciferase driven by a constitutive promoter. Results: Using BLI, we performed imaging of the Plasmodium liver stages of mice infected with PyLuc sporozoites and monitored parasite dissemination during blood-stage infection. Because PyLuc luciferase activity is proportional to the number of parasites, BLI can be used to quantify the effect of drugs on liver-stage development. Moreover, using BLI, we demonstrated that immunization with blood-stage parasites confers partial protective immunity against the development of liver stages. Conclusions: BLI is a noninvasive technique that is useful for screening potential drugs and candidate vaccines with which to combat malaria. The prospect of cross-stage protective immunity increases the number of avenues to be explored in the development of an effective vaccine against malaria.

Original languageEnglish (US)
Pages (from-to)1470-1478
Number of pages9
JournalJournal of Infectious Diseases
Volume200
Issue number9
DOIs
StatePublished - Nov 2009

Fingerprint

Plasmodium
Parasites
Plasmodium yoelii
Liver
Malaria
Vaccines
Immunity
Malaria Vaccines
Firefly Luciferases
Sporozoites
Preclinical Drug Evaluations
Luciferases
Pharmaceutical Preparations
Rodentia
Immunization
Morbidity
Mortality
Infection

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites. / Mwakingwe, Agnes; Ting, Li Min; Hochman, Sarah; Chen, John; Sinnis, Photini; Kim, Kami.

In: Journal of Infectious Diseases, Vol. 200, No. 9, 11.2009, p. 1470-1478.

Research output: Contribution to journalArticle

Mwakingwe, A, Ting, LM, Hochman, S, Chen, J, Sinnis, P & Kim, K 2009, 'Noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites', Journal of Infectious Diseases, vol. 200, no. 9, pp. 1470-1478. https://doi.org/10.1086/606115
Mwakingwe, Agnes ; Ting, Li Min ; Hochman, Sarah ; Chen, John ; Sinnis, Photini ; Kim, Kami. / Noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites. In: Journal of Infectious Diseases. 2009 ; Vol. 200, No. 9. pp. 1470-1478.
@article{7fe26c12d90a400994cba8d253ff1cca,
title = "Noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites",
abstract = "Background: The morbidity and mortality associated with malaria are heightened because of the spread of drug-resistant parasites and the lack of an effective vaccine. Plasmodium liver stages are the targets of new chemotherapeutics and vaccines, but there are limited tools available to study this stage in vivo. Methods: To overcome this obstacle, we developed a method with which to study Plasmodium liver stages by means of bioluminescent imaging (BLI) of the rodent malaria parasite Plasmodium yoelii. We created a P. yoelii YM strain (PyLuc) that stably expresses firefly luciferase driven by a constitutive promoter. Results: Using BLI, we performed imaging of the Plasmodium liver stages of mice infected with PyLuc sporozoites and monitored parasite dissemination during blood-stage infection. Because PyLuc luciferase activity is proportional to the number of parasites, BLI can be used to quantify the effect of drugs on liver-stage development. Moreover, using BLI, we demonstrated that immunization with blood-stage parasites confers partial protective immunity against the development of liver stages. Conclusions: BLI is a noninvasive technique that is useful for screening potential drugs and candidate vaccines with which to combat malaria. The prospect of cross-stage protective immunity increases the number of avenues to be explored in the development of an effective vaccine against malaria.",
author = "Agnes Mwakingwe and Ting, {Li Min} and Sarah Hochman and John Chen and Photini Sinnis and Kami Kim",
year = "2009",
month = "11",
doi = "10.1086/606115",
language = "English (US)",
volume = "200",
pages = "1470--1478",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites

AU - Mwakingwe, Agnes

AU - Ting, Li Min

AU - Hochman, Sarah

AU - Chen, John

AU - Sinnis, Photini

AU - Kim, Kami

PY - 2009/11

Y1 - 2009/11

N2 - Background: The morbidity and mortality associated with malaria are heightened because of the spread of drug-resistant parasites and the lack of an effective vaccine. Plasmodium liver stages are the targets of new chemotherapeutics and vaccines, but there are limited tools available to study this stage in vivo. Methods: To overcome this obstacle, we developed a method with which to study Plasmodium liver stages by means of bioluminescent imaging (BLI) of the rodent malaria parasite Plasmodium yoelii. We created a P. yoelii YM strain (PyLuc) that stably expresses firefly luciferase driven by a constitutive promoter. Results: Using BLI, we performed imaging of the Plasmodium liver stages of mice infected with PyLuc sporozoites and monitored parasite dissemination during blood-stage infection. Because PyLuc luciferase activity is proportional to the number of parasites, BLI can be used to quantify the effect of drugs on liver-stage development. Moreover, using BLI, we demonstrated that immunization with blood-stage parasites confers partial protective immunity against the development of liver stages. Conclusions: BLI is a noninvasive technique that is useful for screening potential drugs and candidate vaccines with which to combat malaria. The prospect of cross-stage protective immunity increases the number of avenues to be explored in the development of an effective vaccine against malaria.

AB - Background: The morbidity and mortality associated with malaria are heightened because of the spread of drug-resistant parasites and the lack of an effective vaccine. Plasmodium liver stages are the targets of new chemotherapeutics and vaccines, but there are limited tools available to study this stage in vivo. Methods: To overcome this obstacle, we developed a method with which to study Plasmodium liver stages by means of bioluminescent imaging (BLI) of the rodent malaria parasite Plasmodium yoelii. We created a P. yoelii YM strain (PyLuc) that stably expresses firefly luciferase driven by a constitutive promoter. Results: Using BLI, we performed imaging of the Plasmodium liver stages of mice infected with PyLuc sporozoites and monitored parasite dissemination during blood-stage infection. Because PyLuc luciferase activity is proportional to the number of parasites, BLI can be used to quantify the effect of drugs on liver-stage development. Moreover, using BLI, we demonstrated that immunization with blood-stage parasites confers partial protective immunity against the development of liver stages. Conclusions: BLI is a noninvasive technique that is useful for screening potential drugs and candidate vaccines with which to combat malaria. The prospect of cross-stage protective immunity increases the number of avenues to be explored in the development of an effective vaccine against malaria.

UR - http://www.scopus.com/inward/record.url?scp=72849131679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72849131679&partnerID=8YFLogxK

U2 - 10.1086/606115

DO - 10.1086/606115

M3 - Article

VL - 200

SP - 1470

EP - 1478

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 9

ER -