Institute of Evolutionary Biology, and Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York, USA.
Parasite Immunol. 2022 Mar;44(3):e12898. doi: 10.1111/pim.12898. Epub 2021 Nov 22.
Malaria parasites exhibit daily rhythms in the intra-erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding-fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how.
We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours and ask whether the density of parasites affects the rescheduling process.
Our experiments reveal parasites shorten the IDC duration by 2-3 hours to become realigned to host feeding-fasting rhythms with 5-6 days, in a density-independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs.
疟原虫在红细胞内发育周期（IDC）中表现出昼夜节律，这为血液中的无性繁殖提供了基础。IDC 时间表与宿主摄食-禁食节律的时间相一致。当 IDC 时间表与宿主节律不匹配时，它很容易重新安排，但目前尚不清楚如何重新安排。
我们在 10 天内密集跟踪四组感染，这些感染在宿主节律和 IDC 时间表之间存在不同的时间对准，在无性密度峰值之前和之后。我们比较对照组感染和被强制调整 12 小时的感染中 IDC 的持续时间、同步性和时间差异，以及寄生虫密度是否影响重新安排过程。
我们的实验表明，寄生虫通过缩短 IDC 持续时间 2-3 小时，以 5-6 天的时间，以与宿主摄食-禁食节律重新对齐，这种方式与密度无关。此外，寄生虫能够在不影响其自身或宿主生存能力的情况下重新安排。了解 IDC 时间表的可塑性程度和限制可能会揭示新的干预目标，例如干扰 IDC 调节的药物和防止 IDC 休眠以提高对现有药物的耐受性。
