Malaria parasite resistance to azithromycin is not readily transmitted by mosquitoes

Antimalarials are now used in combination with partner drugs to stem parasite drug resistance. Partners are often older, safe, cheap drugs, but resistance is already circulating for many, which raises the risk of selecting for multidrug resistance. If the partner drug(s) could be refractory to the spread of resistance, better resistance control could be implemented. We tested whether resistance to the antibiotic azithromycin, which kills malaria parasites by perturbing prokaryote-like protein synthesis in the apicoplast (relict plastid), had fitness costs to the spread of parasites via mosquitoes where parasites are not under drug pressure. Azithromycin resistance mutations in both rodent and human malaria parasites had a negative impact on the ability of resistant parasites to transmit from one vertebrate host to another via mosquitoes. Azithromycin resistance will therefore be less likely to spread geographically, making it an attractive option as a perennial partner compound to protect appropriate frontline antimalarials.