摘要

随着外排活性对结核分枝杆菌耐药性的贡献越来越多，人们越来越重视使用外排抑制剂作为结核病治疗的佐剂。在这里，我们调查了外排活性如何调节monoresistant和多和广泛耐药（M / XDR）结核分枝杆菌临床分离株之间的外排水平。通过存在/不存在外排抑制剂，分子分型和药物抗性相关基因的遗传分析，对该菌株进行抗生素药敏试验。通过实时荧光测定来量化流出活性。结果表明，所有易感或耐药的结核分枝杆菌临床菌株呈现出更快，快速和非特异性外排介导的对药物的短期反应。协同试验表明，外排抑制剂在降低M / XDR菌株的抗性水平方面比单抗菌株更有效。这表明M / XDR菌株与单抗菌株相比，对由外排介导的药物表现出更长的响应，但都将其作为长期应激反应。该工作表明，外排活性调节单抗和M / XDR结核分枝杆菌临床菌株之间的耐药性水平，允许细菌在有毒化合物存在下存活。

With the growing body of knowledge on the contribution of efflux activity to Mycobacterium tuberculosis drug resistance, increased attention has been given to the use of efflux inhibitors as adjuvants of tuberculosis therapy. Here, we investigated how efflux activity modulates the levels of efflux between monoresistant and multi- and extensively drug resistant (M/XDR) M. tuberculosis clinical isolates. The strains were characterized by antibiotic susceptibility testing in the presence/absence of efflux inhibitors, molecular typing, and genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. The results demonstrated that all the M. tuberculosis clinical strains, susceptible or resistant, presented a faster, rapid, and non-specific efflux-mediated short-term response to drugs. The synergism assays demonstrated that the efflux inhibitors were more effective in reducing the resistance levels in the M/XDR strains than in the monoresistant strains. This indicated that M/XDR strains presented a more prolonged response to drugs mediated by efflux compared to the monoresistant strains, but both maintain it as a long-term stress response. This work shows that efflux activity modulates the levels of drug resistance between monoresistant and M/XDR M. tuberculosis clinical strains, allowing the bacteria to survive in the presence of noxious compounds.

http://www.mdpi.com/2079-6382/7/1/18