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Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms [Dataset2]

ABSTRACT: The intra-erythrocytic developmental cycle (IDC) of malaria parasites is synchronized with the time-of-day hosts feed, but the mechanism underpinning this coordination is unknown. Combining in vivo and in vitro approaches using rodent and human malaria parasites, we reveal that: (i) 57% of P. chabaudi genes exhibit 24 h “circadian” periodicity in expression; (ii) 58% of these genes lose rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 9% of P. falciparum genes show circadian expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) is circadian and disrupting it in rodent models shortens the IDC by 2-3 hours; (v) diverse processes, including DNA replication, the ubiquitin and proteasome pathways, are affected by disruption of SR10 and loss of coordination with host rhythms. Our results reveal that malaria parasites are at least in part responsible for scheduling their IDC, explaining the fitness benefits of coordination with host rhythms.

ORGANISM(S): Plasmodium chabaudi chabaudi

PROVIDER: GSE132625 | GEO | 2020/04/20

REPOSITORIES: GEO

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Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

Project description:The intra-erythrocytic developmental cycle (IDC) of malaria parasites is synchronized with the time-of-day hosts feed, but the mechanism underpinning this coordination is unknown. Combining in vivo and in vitro approaches using rodent and human malaria parasites, we reveal that: (i) 57% of P. chabaudi genes exhibit 24 h “circadian” periodicity in expression; (ii) 58% of these genes lose rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of P. falciparum genes show circadian expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) is circadian and disrupting it in rodent models shortens the IDC by 2-3 hours; (v) diverse processes, including DNA replication, the ubiquitin and proteasome pathways, are affected by disruption of SR10 and loss of coordination with host rhythms. Our results reveal that malaria parasites are at least in part responsible for scheduling their IDC, explaining the fitness benefits of coordination with host rhythms.

2020-04-20 | GSE144976 | GEO

Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms [Dataset1]

Project description:The intra-erythrocytic developmental cycle (IDC) of malaria parasites is synchronized with the time-of-day hosts feed, but the mechanism underpinning this coordination is unknown. Combining in vivo and in vitro approaches using rodent and human malaria parasites, we reveal that: (i) 57% of P. chabaudi genes exhibit 24 h “circadian” periodicity in expression; (ii) 58% of these genes lose rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 9% of P. falciparum genes show circadian expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) is circadian and disrupting it in rodent models shortens the IDC by 2-3 hours; (v) diverse processes, including DNA replication, the ubiquitin and proteasome pathways, are affected by disruption of SR10 and loss of coordination with host rhythms. Our results reveal that malaria parasites are at least in part responsible for scheduling their IDC, explaining the fitness benefits of coordination with host rhythms.

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Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms [Dataset2]

Project description:Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms [Dataset2]

| PRJNA548549 | ENA

Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

Project description:Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

| PRJNA548568 | ENA

Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

Project description:Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

| PRJNA605476 | ENA

Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms [Dataset1]

Project description:Malaria parasites regulate intraerythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms [Dataset1]

| PRJNA548570 | ENA

Daily rhythms of Plasmodium chabaudi, showing that 60% of those are intrinsic to the parasite

Project description:Malarial rhythmic fevers are the consequence of the synchronous bursting of red blood cells (RBCs) upon completion of the malaria parasite asexual cell-cycle. Here we hypothesized that an intrinsic clock in the parasite underlies the modulo-24h rhythms of RBC bursting. We show that parasite rhythms are plastic and slow down to match rhythms of hosts with long circadian period. We also demonstrate that malaria rhythms persist even when host food intake is evenly spread across 24h, suggesting that host feeding cues are not required for synchrony. Moreover, we find that the parasite population remains synchronous and rhythmic even in an arrhythmic clock mutant host. Thus, we propose that parasite rhythms are generated by the parasite, possibly to anticipate its rhythmic changing environment.

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Host cell transcripts during malaria liver stage infection reveals a coordinated and sequential set of biological events

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Project description:The blood-stage infection of the malaria parasite, Plasmodium falciparum, exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, triggering 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes, or by a parasite-intrinsic oscillator. To distinguish between hypotheses, we examined the P. falciparum cycle in an in vitro culture system that lacks extrinsic cues from the host and show that P. falciparum has molecular signatures associated with circadian and cell-cycle oscillators. Each of four strains examined has a unique period, indicating strain-intrinsic period control. Finally, we demonstrate that parasites have low cell-to-cell variance in cycle period, on par with a circadian oscillator. We conclude that an intrinsic oscillator is responsible for Plasmodium’s rhythmic life cycle.

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Project description:During infections with malaria parasites P. vivax, patients exhibit rhythmic fevers every 48 hours. These fever cycles correspond with the time parasites take to traverse the Intraerythrocytic Cycle (IEC) and may be guided by a parasite-intrinsic clock. Different species of Plasmodia have cycle times that are multiples of 24 hours, suggesting they may be coordinated with the host circadian clock. We utilized an ex vivo culture of whole blood from patients infected with P. vivax to examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC were correlated across multiple patients, suggesting that the cycles are coupled. In mouse model systems, host-parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable anti-malarial therapies that disrupt this coupling.

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