Data from: Resource limitation prevents the emergence of drug resistance by intensifying within-host competition

Slowing the evolution of antimicrobial resistance is essential if we are to continue to successfully treat infectious diseases. Whether a drug-resistant mutant grows to high densities, and so sickens the patient and spreads to new hosts, is determined by the competitive interactions it has with drug-susceptible pathogens within the host. Competitive interactions thus represent a good target for resistance management strategies. Using an in vivo model of malaria infection, we show that limiting a resource that is disproportionately required by resistant parasites retards the evolution of drug resistance by intensifying competitive interactions between susceptible and resistant parasites. Resource limitation prevented resistance emergence regardless of whether resistant mutants arose de novo or were experimentally added before drug treatment. Our work provides proof of principle that chemotherapy paired with an “ecological” intervention can slow the evolution of resistance to antimicrobial drugs, even when resistant pathogens are present at high frequencies. It also suggests that a broad range of previously untapped compounds could be used for treating infectious diseases.

若要持续有效治疗感染性疾病，延缓抗菌药物耐药性的进化至关重要。耐药突变株能否增殖至高密度水平，进而使患者发病并传播至新宿主，取决于其在宿主体内与药物敏感性病原体之间的竞争互作。因此，竞争互作可作为耐药性管理策略的理想靶点。本研究利用疟疾感染的体内（in vivo）模型，证实限制耐药寄生虫不成比例依赖的营养资源，可通过强化敏感性与耐药性寄生虫之间的竞争互作，延缓抗菌药物耐药性的进化。无论耐药突变株是从头发生（de novo）产生，还是在药物治疗前经实验引入，营养资源限制均可阻止耐药性的出现。本研究从原理上证明，即便耐药病原体已处于高频率存在的状态，化疗联合"生态"干预手段仍可延缓抗菌药物耐药性的进化。该研究同时表明，大量此前未被发掘的化合物可用于感染性疾病的治疗。