Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance.
Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance.
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分枝杆菌氟喹诺酮耐药蛋白 B 是一种新型小 GTP 酶，参与 DNA 旋转酶和耐药性的调节
DOI：
10.1093/nar/gks1351
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发表时间：
2013-02-01
影响因子：
14.9
通讯作者：
Mi K
中科院分区：
文献类型：
--
作者：
Tao J;Han J;Wu H;Hu X;Deng J;Fleming J;Maxwell A;Bi L;Mi K
DNA旋转酶在解决DNA拓扑学问题中起着至关重要的作用，并且是氟喹诺酮类等抗生素的靶标。耻垢分枝杆菌氟喹诺酮耐药蛋白A（MycobacteriumfluoroquinoloneresistanceproteinA，MfPA）是一种新发现的DNA旋转酶抑制剂，被认为是对氟喹诺酮类药物产生内在耐药性的重要因素。然而，MfpA不能阻止药物诱导的体外DNA促旋酶抑制，这意味着其他未知因素的参与。在此，我们发现了一种新的因子，命名为分枝杆菌氟喹诺酮耐药蛋白B（Mfp B），它参与了体内和体外对药物的DNA旋转酶的保护。遗传结果表明，MfpB是必要的MfpA保护DNA促旋酶对药物在体内; mfpB敲除突变体表现出更大的敏感性比野生型的环丙沙星，而过表达MfpA和MfpB的菌株表现出更高的敏感性损失。进一步的生化特性表明MfpB是一个小的GTP酶，它的GTP结合形式直接与MfpA相互作用，并影响其与DNA旋转酶的相互作用。MfpB中降低其GTdR活性的突变破坏其保护功效。我们的研究表明，MfpB，一个小的GTP酶，需要MfpA赋予的DNA促旋酶的保护。
DNA gyrase plays a vital role in resolving DNA topological problems and is the target of antibiotics such as fluoroquinolones. Mycobacterium fluoroquinolone resistance protein A (MfpA) from Mycobacterium smegmatis is a newly identified DNA gyrase inhibitor that is believed to confer intrinsic resistance to fluoroquinolones. However, MfpA does not prevent drug-induced inhibition of DNA gyrase in vitro, implying the involvement of other as yet unknown factors. Here, we have identified a new factor, named Mycobacterium fluoroquinolone resistance protein B (MfpB), which is involved in the protection of DNA gyrase against drugs both in vivo and in vitro. Genetic results suggest that MfpB is necessary for MfpA protection of DNA gyrase against drugs in vivo; an mfpB knockout mutant showed greater susceptibility to ciprofloxacin than the wild-type, whereas a strain overexpressing MfpA and MfpB showed higher loss of susceptibility. Further biochemical characterization indicated that MfpB is a small GTPase and its GTP bound form interacts directly with MfpA and influences its interaction with DNA gyrase. Mutations in MfpB that decrease its GTPase activity disrupt its protective efficacy. Our studies suggest that MfpB, a small GTPase, is required for MfpA-conferred protection of DNA gyrase.
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影响因子：
5
作者：
Collin, Frederic;Karkare, Shantanu;Maxwell, Anthony
通讯作者：
Maxwell, Anthony
影响因子：
3.7
作者：
Laponogov I;Pan XS;Veselkov DA;McAuley KE;Fisher LM;Sanderson MR
通讯作者：
Sanderson MR
影响因子：
3.3
作者：
Martínez, LJ;Sik, RH;Chignell, CF
通讯作者：
Chignell, CF
DOI：
10.1073/pnas.0401595101
发表时间：
2004-05-11
影响因子：
11.1
作者：
Corbett, KD;Shultzaberger, RK;Berger, JM
通讯作者：
Berger, JM
影响因子：
5.6
作者：
Loris, R;Dao-Thi, MH;Wyns, L
通讯作者：
Wyns, L