Successful treatment of tuberculosis (TB) depends on the eradication of its causative agent Mycobacterium tuberculosis (Mtb) in the host. However, the emergence of phenotypically drug-resistant Mtb in the host environment tempers the ability of antibiotics to cure disease. Host immunity produces diverse microenvironmental niches that are exploited by Mtb to mobilize adaptation programs. Such differential interactions amplify pre-existing heterogeneity in the host–pathogen milieu to influence disease pathology and therapy outcome. Therefore, comprehending the intricacies of phenotypic heterogeneity can be an empirical step forward in potentiating drug action. With this goal, we review the interconnectedness of the lesional, cellular, and bacterial heterogeneity underlying phenotypic drug resistance. Based on this information, we anticipate the development of new therapeutic strategies targeting host–pathogen heterogeneity to cure TB.

结核病 (TB) 的成功治疗取决于在宿主中根除其病原体结核分枝杆菌( Mtb )。然而，宿主环境中表型耐药Mtb 的出现削弱了抗生素治愈疾病的能力。宿主免疫产生多种被Mtb开发的微环境生态位动员适应计划。这种不同的相互作用放大了宿主-病原体环境中预先存在的异质性，以影响疾病病理学和治疗结果。因此，理解表型异质性的复杂性可以成为增强药物作用的经验性步骤。带着这个目标，我们回顾了表型耐药性背后的病变、细胞和细菌异质性之间的相互联系。基于这些信息，我们预计将开发针对宿主 - 病原体异质性的新治疗策略来治愈结核病。