Spiroketal indolyl Mannich bases (SIMBs) present a novel class of membrane-inserting antimycobacterials with efficacy in a tuberculosis mouse model. SIMBs exert their antibacterial activity by two mechanisms. The indolyl Mannich base scaffold causes permeabilization of bacteria, and the spiroketal moiety contributes to inhibition of the mycolic acid transporter MmpL3. Here, we show that low-level resistance to SIMBs arises by mutations in the transcriptional repressor MmpR5, resulting in upregulation of the efflux pump MmpL5.

中文翻译：

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通过上调结核分枝杆菌中的MmpL5对插入膜的MmpL3抑制剂的耐药性。

螺旋螺吲哚基曼尼希碱（SIMBs）提出了一类新型的膜插入抗分枝杆菌药，在结核病小鼠模型中具有功效。SIMB通过两种机制发挥其抗菌活性。吲哚基曼尼希碱基支架引起细菌的通透性，螺环部分有助于抑制霉菌酸转运蛋白MmpL3。在这里，我们表明对SIMBs的低水平耐药性是由转录阻遏物MmpR5中的突变引起的，导致外排泵MmpL5的上调。