Stress, drugs and the evolution of reproductive restraint in malaria parasites

Abstract

Life-history theory predicts that sexually reproducing organisms have evolved to resolve resource-allocation trade-offs between growth/survival versus reproduction, and current versus future reproduction. Malaria parasites replicate asexually in their vertebrate hosts, but must reproduce sexually to infect vectors and be transmitted to new hosts. As different specialized stages are required for these functions, the division of resources between these life-history components is a fundamental evolutionary problem. Here, we test how drug-sensitive and drug-resistant isolates of the human malaria parasite Plasmodium falciparum resolve the trade-off between in-host replication and between-host transmission when exposed to treatment with anti-malarial drugs. Previous studies have shown that parasites increase their investment in sexual stages when exposed to stressful conditions, such as drugs. However, we demonstrate that sensitive parasites facultatively decrease their investment in sexual stages when exposed to drugs. In contrast to previous studies, we tested parasites from a region where treatment with anti-malarial drugs is common and transmission is seasonal. We hypothesize that when exposed to drugs, parasites invest in their survival and future transmission by diverting resources from reproduction to replication. Furthermore, as drug-resistant parasites did not adjust their investment when exposed to drugs, we suggest that parasites respond to changes in their proliferation (state) rather the presence of drugs.

Figure 1.

Means ± s.e. gametocyte conversion rates (calculated as the proportion of ring stages from each asexually produced cohort that committed to becoming gametocytes) observed during cultures for drug-sensitive and drug-resistant isolates when exposed to anti-malarial drugs or control conditions. Conversion rate significantly differed according to whether parasites were ‘safe’ or ‘vulnerable’ to any drugs in their cultures. Parasites safe from treatment included those in control cultures (white squares, sensitive lines; white circles, resistant lines) and resistant parasites in drug-treated cultures (black circle), whereas vulnerable parasites are the drug-sensitive parasites exposed to drugs (black squares). Therefore, only the sensitive parasites altered their conversion rates when exposed to drugs. Best-fit lines are from the minimum adequate model for parasites vulnerable to drugs (solid line) and safe from drugs (dashed line).

Figure 2.

(a) Means ± s.e. per cent of RBCs infected with gametocytes (gametocytaemia) and (b) ring-stage asexually produced parasites (parasitaemia) during cultures for drug-sensitive (squares) and drug-resistant (circles) lines when exposed to anti-malarial drugs (black symbols) or control conditions (white symbols).