Efflux pumps of the resistance-nodulation-division family: a perspective of their structure, function, and regulation in gram-negative bacteria.
Efflux pumps of the resistance-nodulation-division family: a perspective of their structure, function, and regulation in gram-negative bacteria.
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DOI：
10.1002/9780470920541.ch3
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发表时间：
2011
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随着青霉素的首次发现和随后在20世纪40年代大规模生产抗生素，感染细菌迅速适应并对有害分子产生抗药性。事实上，1947年发表的一份报告发现，在测试的100种葡萄球菌感染中，有38种被归类为对青霉素高度耐药(1)。最初的耐药性主要与个别酶灭活特定的抗生素有关，如青霉素上的β内酰胺酶。随着新型抗生素被应用来对抗耐药病原体，选择性压力导致了根本上新的耐药方法。目前，细菌利用三种主要机制来逃避杀生剂的毒性作用。这些机制包括修饰药物的酶，抗菌靶标的改变，以及由于外排泵的存在或孔蛋白表达减少而导致的药物摄取减少。酶修饰涉及两类酶，包括那些降解特定抗生素的酶(2)和化学修饰抗菌化合物的酶(3)，从而导致药物功能的抑制。细菌使用的第二种机制是改变药物靶标。几乎所有相关的氟喹诺酮耐药都归因于靶点改变，即特定的突变抑制药物与DNA旋转酶和拓扑异构酶IV(4)的相互作用。虽然
With the initial discovery of penicillin and the ensuing mass production of antibiotics in the 1940s, infectious bacteria quickly adapted and developed resistance to the deleterious molecules. In fact, a report published in 1947 found that of 100 staphylococcus infections tested, 38 were classified as highly resistant to penicillin (1). The initial resistance was primarily associated with individual enzymes inactivating specific antibiotics, such as βlactamases on penicillin. As novel antibiotics were implemented to combat resistant pathogens, selective pressure led to fundamentally new methods of drug resistance. Currently, there are roughly three major mechanisms utilized by bacteria to evade the toxic effects of biocidal agents. These mechanisms include enzymes that modify the drug, alteration of the antibacterial target, and reduced drug uptake due to the presence of efflux pumps or a decrease in porin expression. Enzymatic modification involves two classes of enzymes, including those that degrade specific antibiotics (2) and enzymes that chemically modify the antibacterial compound (3), resulting in inhibition of drug function. The second mechanism employed by bacteria is alteration of the drug target. Nearly all relevant fluoroquinolone resistance has been attributed to target alteration, whereby specific mutations inhibit the drugs interaction to DNA gyrase and topoisomerase IV (4). Although