Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru-560012, India; Centre for Infectious Disease and Research (CIDR), Indian Institute of Science, Bengaluru-560012, India.
Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru-560012, India; Centre for Infectious Disease and Research (CIDR), Indian Institute of Science, Bengaluru-560012, India.
Trends Microbiol. 2021 Jul;29(7):606-620. doi: 10.1016/j.tim.2020.10.013. Epub 2020 Dec 10.
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.
成功治疗结核病（TB）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。宿主免疫产生了多种微环境小生境，Mtb 利用这些小生境来调动适应程序。这种差异相互作用放大了宿主-病原体环境中预先存在的异质性，从而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为增强药物作用迈出有意义的一步。为此，我们综述了导致表型耐药的病变、细胞和细菌异质性之间的相互关系。在此基础上，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疗结核病。
