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

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. Overall design: Hosts were 6-8 weeks old female MF1 mice housed in groups of five at 21°C with food and drinking water supplemented with 0.05 % para-aminobenzoic acid (PABA, to supplement parasite growth) provided ad libitum. All experimental infections were initiated by intravenous injection of 1 x 107 P. chabaudi (clone AS) parasitized red blood cells. Parasites at ring stage were collected at ZT0.5 (08:00 GMT) from donor mice housed in standard LD light conditions (Lights ON 07:30; Lights OFF 19:30 GMT) and immediately used to infect two groups of experimental mice. One group (termed “matched”) were entrained to the same photoperiod as the donor mice, generating infections in which parasite and host rhythms were in the same phase. The other group (termed “mismatched”) were entrained to reverse light (Lights OFF 07:30 and Lights ON 19:30 GMT) resulting in infections in which the parasite is out of phase with the host by 12 hours. Samples were collected every three hours, over a period of 30 hours, from 09:00 GMT on day 4 to 15:00 GMT on day 5 post infection. This corresponds to a starting time of ZT1.5 for matched, and ZT13.5 for mismatched infections.