近日，加拿大不列颠哥伦比亚大学的微生物学家发现一个用于治疗寄生虫病的药物有潜力治疗肺结核（TB）。这项研究结果发表在本周的Antimicrobial Agents and Chemotherapy杂志上。
近40年前发现，发展中国家常用阿维菌素(Avermectin)类药物，以消除寄生型蠕虫。在不列颠哥伦比亚大学的研究中表明，该药物可以杀死导致结核病的细菌，甚至包括耐药形式。
不列颠哥伦比亚大学研究人员目前正在进行动物模型，以确定有效的剂量水平和治疗方案。他们还将研究是否阿维菌素可以与其他药物相结合，以创建更有效的治疗方法。
Functional and Genetic Characterization of the Tap Efflux Pump in Mycobacterium bovis BCG
Santiago Ramón-García,et al.
Efflux pumps extrude a wide variety of chemically unrelated compounds conferring multidrug resistance and participating in numerous physiological processes. Mycobacterium tuberculosis possesses many efflux pumps, and their roles in drug resistance and physiology are actively investigated. In this work we found that tap mutant cells showed changes in morphology and a progressive loss of viability upon subcultivation in liquid medium. Transcriptome analysis in Mycobacterium bovis BCG revealed that disruption of the Rv1258c gene, encoding the Tap efflux pump, led to an extensive change in gene expression patterns during stationary phase, with no changes during exponential growth. In stationary phase, Tap inactivation triggered a general stress response and led to a general repression of genes involved in cell wall biosynthesis, in particular the formation of the peptidoglycan; this suggested the accumulation of an unknown Tap substrate that reaches toxic concentrations during stationary phase. We also found that both disruption and overexpression of tap altered susceptibility to many clinically approved antibiotics in M. bovis BCG. Acriflavine and tetracycline accumulation assays and carbonyl cyanide m-chlorophenylhydrazone (CCCP) potentiation experiments demonstrated that this phenotype was due to an active efflux mechanism. These findings emphasize the important role of the Tap efflux pump in bacterial physiology and intrinsic drug resistance.
