肺结核分枝杆菌的遗传机制和抗结核药物的表型耐药性

Title:Human Tuberculosis II. M. tuberculosis Mechanisms of Genetic and Phenotypic Resistance to Anti-Tuberculosis Drugs

Volume: 23 Issue: 12

Author(s): Giampietro Sgaragli, Maria Frosini

Affiliation:

关键词: 遗传表型耐药，毒素-抗毒素模型，DosR调节子，药物外排泵，细菌持续存在，代谢适应。

摘要: The great progress of knowledge of both M. tuberculosis physiology and how human host and bacilli interact has provided fertile ground for improving diagnosis and cure of TB infection. Once M. tuberculosis has infected humans, it elaborates strategies for evading the risk to killing by the cells of the host immune system and by the anti-tuberculosis (anti-TB) agents employed to cure infection. These strategies give rise to a bacterial multidrug resistance (MDR) status. This stems firstly from genetic mutations targeting a constellation of drug-processing mechanisms that still need full identification, as drug efflux pumps and drug activating/ inactivating enzymes (genetic resistance). Secondly, from the bacterial adaptation to stressful environmental conditions by adopting a temporary dormancy state lasting for decades and characterized by indifference to anti-TB drugs (phenotypic resistance or tolerance). The clarification of the strategies elaborated for surviving by M. tuberculosis has brought to the identification in the last few years of a number of mycobacterial molecular targets worth to exploitation for the development of novel and powerful anti-TB drugs. These targets include drug-efflux pump systems, considered partly responsible for genetic multi-drug resistance, and several enzymes and pump systems, as well, that sustain the metabolic adaptations of M. tuberculosis in the host and give rise to its phenotypic drug resistance.

Cite this article as:

Giampietro Sgaragli, Maria Frosini , Human Tuberculosis II. M. tuberculosis Mechanisms of Genetic and Phenotypic Resistance to Anti-Tuberculosis Drugs, Current Medicinal Chemistry 2016; 23 (12) . https://dx.doi.org/10.2174/0929867323666160405112820