Lipoprotein Processing Is Essential for Resistance of Mycobacterium tuberculosis to Malachite Green
Lipoprotein Processing Is Essential for Resistance of Mycobacterium tuberculosis to Malachite Green
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DOI：
10.1128/aac.00647-09
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发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Ernst, Joel D.
中科院分区：
文献类型：
--
作者：
Banaei, Niaz;Kincaid, Eleanor Z.;Ernst, Joel D.
孔雀石绿是一种合成抗菌染料，50 多年来一直在分枝杆菌培养基中用于抑制污染物的生长。分枝杆菌对孔雀石绿的抗性的分子基础尚不清楚，尽管已经表明细胞被膜中存在孔雀石绿还原酶。本研究的目的是探讨脂蛋白在结核分枝杆菌对孔雀石绿耐药性中的作用。研究了结核分枝杆菌脂蛋白信号肽酶 II (lspA) 突变体 (Delta lspA::lspA(mut)) 在含有和不含 1 mg/L 孔雀石绿的 Middlebrook 琼脂上的复制。还比较了lspA突变体与野生型结核分枝杆菌的孔雀石绿脱色率以及对十二烷基硫酸钠(SDS)洗涤剂和一线抗结核药物的敏感性。 lspA 突变体在带有孔雀石绿的 Middlebrook 琼脂上的 CFU 形成效率降低了 10(4) 倍。在 lspA 突变体存在的情况下，孔雀石绿的脱色速度比野生型细菌更快。 lspA 突变体对 SDS 去污剂高度敏感，并且对一线抗结核药物表现出更高的敏感性。总之，LspA 的脂蛋白加工对于结核分枝杆菌对孔雀石绿的抗性至关重要。细胞壁通透性缺陷可能是 lspA 突变体对孔雀石绿过敏的原因。
Malachite green, a synthetic antimicrobial dye, has been used for over 50 years in mycobacterial culture medium to inhibit the growth of contaminants. The molecular basis of mycobacterial resistance to malachite green is unknown, although the presence of malachite green-reducing enzymes in the cell envelope has been suggested. The objective of this study was to investigate the role of lipoproteins in resistance of Mycobacterium tuberculosis to malachite green. The replication of an M. tuberculosis lipoprotein signal peptidase II (lspA) mutant (Delta lspA::lspA(mut)) on Middlebrook agar with and without 1 mg/liter malachite green was investigated. The lspA mutant was also compared with wild-type M. tuberculosis in the decolorization rate of malachite green and sensitivity to sodium dodecyl sulfate (SDS) detergent and first-line antituberculosis drugs. The lspA mutant has a 10(4)-fold reduction in CFU-forming efficiency on Middlebrook agar with malachite green. Malachite green is decolorized faster in the presence of the lspA mutant than wild-type bacteria. The lspA mutant is hypersensitive to SDS detergent and shows increased sensitivity to first-line antituberculosis drugs. In summary, lipoprotein processing by LspA is essential for resistance of M. tuberculosis to malachite green. A cell wall permeability defect is likely responsible for the hypersensitivity of lspA mutant to malachite green.