Abstract
Background: Malaria parasite species differ greatly in the harm they do to humans. While P. falciparum kills hundreds of thousands per year, P. vivax kills much less often and P. malariae is relatively benign. Strains of the rodent malaria parasite Plasmodium chabaudi show phenotypic variation in virulence during infections of laboratory mice. This make it an excellent species to study genes which may be responsible for this trait. By understanding the mechanisms which underlie differences in virulence we can learn how parasites adapt to their hosts and how we might prevent disease. Methods: Here we present a complete reference genome sequence for a more virulent P. chabaudi strain, PcCB, and perform a detailed comparison with the genome of the less virulent PcAS strain. Results: We found the greatest variation in the subtelomeric regions, in particular amongst the sequences of the pir gene family, which has been associated with virulence and establishment of chronic infection. Despite substantial variation at the sequence level, the repertoire of these genes has been largely maintained, highlighting the requirement for functional conservation as well as diversification in host-parasite interactions. However, a subset of pir genes, previously associated with increased virulence, were more highly expressed in PcCB, suggesting a role for this gene family in virulence differences between strains. We found that core genes involved in red blood cell invasion have been under positive selection and that the more virulent strain has a greater preference for reticulocytes, which has elsewhere been associated with increased virulence. Conclusions: These results provide the basis for a mechanistic understanding of the phenotypic differences between Plasmodium chabaudi strains, which might ultimately be translated into a better understanding of malaria parasites affecting humans.
Highlights
Malaria is a disease caused by parasites of the genus Plasmodium
MT P. chabaudi CB is more virulent than the AS strain in C57BL/6 mice and sequesters more in the lungs Previous experiments have shown that, in infections established by serially blood passaged (SBP), PcCB is more virulent than PcAS (Cheesman et al, 2006; Lamb & Langhorne, 2008; Lin et al, 2017) and that after mosquito transmission (MT), blood-stage parasitemia with either PcCB and PcAS is considerably lower than infections initiated with SBP parasites (Spence et al, 2013)
The rodent malaria parasite Plasmodium chabaudi is a good model for understanding the interactions between the parasite and its host
Summary
Malaria is a disease caused by parasites of the genus Plasmodium. While some species are highly virulent, frequently causing disease and often death, others are usually asymptomatic. Four such species (Plasmodium yoelii, P. berghei, P. chabaudi and P. vinckei), isolated from wild thicket rats in Africa, have been adapted to grow in laboratory rodents While these species reproduce many of the biological and pathological characteristics of human malaria parasites, P. chabaudi is the only species that produces a chronic blood-stage infection in laboratory mice. Several strains of P. chabaudi have been isolated, which give rise to infections with differing parasite burdens and severity of clinical manifestations (Cheesman et al, 2006; Lamb & Langhorne, 2008; Mackinnon & Read, 1999) They could provide good models to determine parasite and host contributions to virulence
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