# Experimental evolution of Plasmodium yoelii in single and helminth-coinfected mice

## TL;DR

This study shows how the malaria parasite Plasmodium yoelii adapts when infecting mice alone or alongside a worm parasite, affecting its replication and virulence.

## Contribution

The study experimentally evolves Plasmodium yoelii in coinfected and single-infected hosts to assess adaptation and virulence changes.

## Key findings

- Serial passages increased parasitemia and virulence due to faster-replicating genotypes.
- Evolved lines showed slower replication in mismatched infection environments.
- No strong divergence in virulence between single and coinfected host-evolved lines.

## Abstract

Coinfection has the potential to affect key traits describing the infection dynamics, the severity of the disease and in fine parasite fitness. However, despite its pervasiveness, experimental work investigating how parasites adapt to the conditions provided by a coinfected host is mostly missing.

We adopted an experimental evolution approach to investigate if coinfection with the nematode Heligmosomoides polygyrus (Hp) affected the infection dynamics and virulence of the murine malaria parasite Plasmodium yoelii (Py). To this purpose, lines of Py were passaged either in single infected hosts (SI-lines) or in hosts that had been previously infected with Hp (COI-lines). After five and seven passages, the infection dynamics and virulence of evolved lines were compared to the ancestral Py population during single infection trials. COI-lines were also used to infect hosts during coinfection trials, allowing us to compare within-host Py replication when the environment during the evaluation trials matched the environment experienced during the passages and when the two environments were mismatched.

We found that serial passages increased parasitemia and Py virulence, due to the competitive advantage of genotypes with the fastest replication rate, but SI-lines and COI-lines had relatively similar replication rate and virulence. Hosts infected with evolved lines of Py were also less tolerant (steeper slope between red blood cell counts and parasitemia) but there was no difference between SI-lines and COI-lines. Finally, we found that when COI-lines were used during single infection trials (mismatched environments), they had a slower early replication rate compared to matched-environment trials.

We did not find strong evidence supporting a divergence between the virulence of SI-lines and COI-lines, possibly due to the cost of virulence paid by COI-lines. However, Py rapidly adapted to the environmental conditions provided by single infected or coinfected hosts, as shown by the slower replication rate found in mismatched-environment trials.

The online version contains supplementary material available at 10.1186/s12936-025-05764-1.