Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones.
Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones.
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DOI：
10.1038/srep11910
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发表时间：
2015-07-03
影响因子：
4.6
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Li Q;Xie L;Long Q;Mao J;Li H;Zhou M;Xie J
抗生素耐药性对全球公共卫生构成灾难性威胁。对潜在作用机制的新见解将激发更好的控制耐药性的措施。氟喹诺酮类药物是一种强效且广泛使用的广谱抗生素。细菌蛋白质降解途径代表了新型抗生素开发的新药物靶点。分枝杆菌蛋白酶体辅助因子C（pafC）是细菌蛋白酶体的一个组成部分，与细菌对氟喹诺酮类药物的耐药性有关。PafC缺失突变体对氟喹诺酮类药物（包括诺氟沙星、诺氟沙星、氧氟沙星、环丙沙星）过敏，但对其他抗生素（如异烟肼、利福平、壮观霉素、氯霉素、卷曲霉素）不过敏。这种表型可以通过互补作用恢复。pafC突变体对H2O2暴露超敏感。铁螯合剂（联吡啶）和羟基自由基清除剂（硫脲）可以消除这种差异。pafC是一种新型内在选择性耐药基因的发现，为细菌蛋白质降解途径作为开发新型抗生素的可药用靶点提供了新的证据。
Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics.
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