A combinatorial genetics approach reveals limits to redundancy within Plasmodium falciparum invasion ligand families

Two protein families, the Erythrocyte binding-like (EBA) and Reticulocyte binding-like (Rh) proteins, are known to play a key role in invasion of human red blood cells by Plasmodium falciparum parasites. This study systematically tested the viability of all possible combinations of EBA and Rh null mutants to identify pairs of genes which when disrupted together were more detrimental to parasite survival. A pooled transfection approach combined with next generation sequencing was used to assess double mutant viability, before individual double, and in some cases triple, mutant lines were generated using traditional approaches.