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Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy.

ABSTRACT: Relapses of Plasmodium dormant liver hypnozoites compromise malaria eradication efforts. New radical cure drugs are urgently needed, yet the vast gap in knowledge of hypnozoite biology impedes drug discovery. We previously unraveled the transcriptome of 6 to 7 day-old P. cynomolgi liver stages, highlighting pathways associated with hypnozoite dormancy (Voorberg-van der Wel et al., 2017). We now extend these findings by transcriptome profiling of 9 to 10 day-old liver stage parasites, thus revealing for the first time the maturation of the dormant stage over time. Although progression of dormancy leads to a 10-fold decrease in transcription and expression of only 840 genes, including genes associated with housekeeping functions, we show that pathways involved in quiescence, energy metabolism and maintenance of genome integrity remain the prevalent pathways active in mature hypnozoites.

SUBMITTER: Bertschi NL

PROVIDER: S-EPMC6344078 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy.

Bertschi Nicole L NL Voorberg-van der Wel Annemarie A Zeeman Anne-Marie AM Schuierer Sven S Nigsch Florian F Carbone Walter W Knehr Judith J Gupta Devendra K DK Hofman Sam O SO van der Werff Nicole N Nieuwenhuis Ivonne I Klooster Els E Faber Bart W BW Flannery Erika L EL Mikolajczak Sebastian A SA Chuenchob Vorada V Shrestha Binesh B Beibel Martin M Bouwmeester Tewis T Kangwanrangsan Niwat N Sattabongkot Jetsumon J Diagana Thierry T TT Kocken Clemens Hm CH Roma Guglielmo G

eLife 20181227

Relapses of Plasmodium dormant liver hypnozoites compromise malaria eradication efforts. New radical cure drugs are urgently needed, yet the vast gap in knowledge of hypnozoite biology impedes drug discovery. We previously unraveled the transcriptome of 6 to 7 day-old P. cynomolgi liver stages, highlighting pathways associated with hypnozoite dormancy (Voorberg-van der Wel et al., 2017). We now extend these findings by transcriptome profiling of 9 to 10 day-old liver stage parasite ...[more]

PMID: 30589413

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Project description:Plasmodium cynomolgi (Pcy), a simian malaria parasite, is a recent perfect example of emerging zoonotic transfer in human. This review summarizes the current knowledge on the epidemiology of natural Pcy infections in humans, mosquitoes and monkeys, along with its biological, clinical and drug sensitivity patterns. Knowledge gaps and further studies on Pcy in humans are also discussed. This parasite currently seems to be geographically limited in South-East Asia (SEA) with a global prevalence in human ranging from 0 to 1.4%. The Pcy infections were reported in local SEA populations and European travelers, and range from asymptomatic carriage to mild/moderate attacks with no evidence of pathognomonic clinical and laboratory patterns but with Pcy strain-shaped clinical differences. Geographical distribution and competence of suitable mosquito vectors and non-primate hosts, globalization, climate change, and increased intrusion of humans into the habitat of monkeys are key determinants to emergence of Pcy parasites in humans, along with its expansion outside SEA. Sensitization/information campaigns coupled with training and assessment sessions of microscopists and clinicians on Pcy are greatly needed to improve data on the epidemiology and management of human Pcy infection. There is a need for development of sensitive and specific molecular tools for individual diagnosis and epidemiological studies. The development of safe and efficient anti-hypnozoite drugs is the main therapeutic challenge for controlling human relapsing malaria parasites. Experience gained from P. knowlesi malaria, development of integrated measures and strategies-ideally with components related to human, monkeys, mosquito vectors, and environment-could be very helpful to prevent emergence of Pcy malaria in humans through disruption of transmission chain from monkeys to humans and ultimately contain its expansion in SEA and potential outbreaks in a context of malaria elimination.

Dataset Information

Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite Plasmodium cynomolgi during progression into dormancy.

Publications

Transcriptomic analysis reveals reduced transcriptional activity in the malaria parasite <i>Plasmodium cynomolgi</i> during progression into dormancy.

Similar Datasets

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