A study co-led by ICREA researcher at ISGlobal Alfred Cortés and scientists at the Institute of Tropical Medicine (ITM) in Antwerp found that parasites infecting humans use only one gene of the clag3 family at the time, which is not the same as the one used by parasites cultured in the laboratory, and that these expression patterns are reset before starting infection of a new host. The results, published in the Journal of Infectious Diseases, support the idea that genes that are switched on in some parasites and switched off in others (clonally variant genes) facilitate the adaptation of P. falciparum parasites to different environmental conditions.
During its life cycle, the malaria parasite needs to adapt to fluctuating environmental conditions such as nutrient concentrations, presence of drugs, fever or immune responses by the host. Adaptation involves natural selection of parasites that use their variant genes in a way that confers fitness under the new environment conditions. These genes are regulated through so-called epigenetic mechanisms, which allow transmission to the next generation.
One example are the clag3 genes (3.1 and 3.2), which are involved in nutrient uptake. Cortes’ research team had already described that switches between alternative states (expression of one gene, of the other, or of none) can occur spontaneously among cultured parasites, permitting constant generation of diversity within the parasite population. However, little was known of clag3 expression during human infections.
In this study, the authors analysed blood samples obtained from returning travellers attending clinics in Antwerp and from children in The Gambia, as well as samples from experimentally-infected human volunteers. They found that parasites infecting humans use only one gene of the family at the time, which is not the same as the one most commonly used by the parasite in culture. Changing parasites from human blood conditions to culture conditions or vice versa, or exposing parasites to a toxic compound, results in switches in clag3 expression. They also found that expression patterns are reset before starting infection of a new host (i.e. the epigenetic memory is erased), resulting in a diverse population of parasites and thus increasing its probabilities of survival in a new human host with unpredictable conditions.
“These results support the idea that clonally variant genes such as clag3 play an important role in parasite adaptation” explains Sofía Mira-Martinez, first author of the study and a TransGlobal Health awardee, “and provide a first insight into how these genes are used during human infection”.
The Barcelona Institute for Global Health is supported by the “la Caixa” Foundation.
Mira-Martinez S, van Schuppen E, Amambua-Ngwa A, et al. Expression of the Plasmodium falciparum clonally variant clag3 genes in human infections. J Infect Dis jix053, 07 February 2017