Rv1258c acts as a drug efflux pump and growth controlling factor in Mycobacterium tuberculosis
Rv1258c acts as a drug efflux pump and growth controlling factor in Mycobacterium tuberculosis
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Rv1258c 在结核分枝杆菌中充当药物外排泵和生长控制因子
DOI：
10.1016/j.tube.2022.102172
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Zhaogang Sun
中科院分区：
文献类型：
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作者：
Hongbing Jia;Hongqian Chu;Guangming Dai;Tingming Cao;Zhaogang Sun
外排作为结核分枝杆菌存活机制的可能作用（M.结核病）正受到越来越多的关注。此前，已知Rv 1258 c（Tap）及其某些突变可产生临床相关的耐药性。在本研究中，我们在G195 C、T297 P和I328 T中发现了Rv 1258 c的新突变。通过基因敲除和补体调节T297 P和I328 T对M耐药性的影响tb H37 Rv表明M. tb Δ Rv 1258 c对利福平、乙胺丁醇、氧氟沙星、阿米卡星、卷曲霉素和链霉素的MIC略低于M. tb H37 Rv WT和补体。Rv 1258 c T297 P和Rv 1258 c I328 T对乙胺丁醇和卷曲霉素耐药性的影响大于Rv 1258 c WT的补体。最重要的是，M。tb Δ Rv 1258 c在正常培养基中生长缓慢。基于TMT的M. tb Δ Rv 1258 c和WT结果表明，Rv 1258 c的敲除使核糖体系统和特殊的五种VII型分泌系统之一ESX-3的表达显著下调，从而使细菌生长受到损害。这些结果表明，新发现的Rv 1258 c的T297 P和I328 T突变有助于对乙胺丁醇和卷曲霉素的耐药性增加。Rv 1258 c作为生长控制因子影响M. TB.
The possible role of efflux as a survival mechanism in Mycobacterium tuberculosis (M. tb) is gaining an increasing attention. Previously, Rv1258c (Tap) and its certain mutations have been known to confer the clinically relevant drug resistance. In this study, we found new mutations of Rv1258c in G195C, T297P and I328T. Effect of modulating T297P and I328T on the drug resistance by knockout and complement in M. tb H37Rv showed that M. tb ΔRv1258c showed a slightly lower MIC of rifampin, ethambutol, ofloxacin, amikacin, capreomycin and streptomycin than M. tb H37Rv WT and the complement. Rv1258c T297P and Rv1258c I328T affected the drug resistance of ethambutol and capreomycin more than the complement of Rv1258c WT. Most importantly, M. tb ΔRv1258c exhibited a slow growth in the normal culture medium. TMT-based quantitative proteomics analysis of M. tb ΔRv1258c and WT showed that the knockout of Rv1258c greatly down-regulated the expression of ribosome system and one of the special five type VII secretion systems, ESX-3, which impaired the bacterial growth. These results indicate that newly found T297P and I328T mutation of Rv1258c contribute to more resistant to ethambutol and capreomycin. And Rv1258c as growth controlling factor influences the growth of M. tb.