Mistimed malaria parasites re-synchronize with host feeding-fasting rhythms by shortening the duration of intra-erythrocytic development.

Aidan J O’Donnell,Sarah E Reece,Megan A Greischar

doi:10.1111/pim.12898

Aidan J O’Donnell, Sarah E Reece + Show 1 more

Open Access

https://doi.org/10.1111/pim.12898

Copy DOI

Abstract

AimsMalaria 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.MethodsWe 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.Results and conclusionsOur 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.

Highlights

Biological rhythms enable organisms to undertake activities at the time of day they are best undertaken
By analysing ~1200 samples, we demonstrate that phenotypic plasticity in the intra-erythrocytic development cycle (IDC) duration allows P. chabaudi to recover from a ~12-hour mismatch to host feeding-fasting rhythms within approximately 5–6 days (Figures 3 and 4), in a manner independent of parasite density (Figure 5)
Whilst our aim was to investigate the ecology surrounding rescheduling of the IDC, we tested whether this process has longer-term consequences throughout infections

Summary

| INTRODUCTION

Biological rhythms enable organisms to undertake activities at the time of day they are best undertaken. When the timing of the IDC schedule is out of synchrony with the host, parasites suffer losses in the number of both asexually replicating stages and sexual transmission stages27-29 are more vulnerable to antimalarial drug treatment,[30] and gene expression patterns underpinning key cellular processes are significantly altered.[25] P. chabaudi's IDC schedule allows parasites to maximally exploit rhythmicity in the resources they require from the host's food.[20] Conveniently, this schedule ensures the maturation of sexual stages coincides with the time-of- day vectors forage for blood.[31]. P. chabaudi recovers from a 12-hour mismatch to the host's feeding-fasting rhythm within 5–7 IDCs.[19,29] During natural infections, parasites may benefit from a time-keeping ability if egress from the liver to initiate blood stage replication occurs asynchronously or at a different time of day to optimal for IDC stages. Understanding the extent of, and limits on, plasticity in the IDC schedule is important because asexual replication is responsible for the severe symptoms of malaria and fuels the production of sexual transmission stages and conferring tolerance to antimalarials.[4,35]

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION