Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time.
Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time.
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DOI：
10.3390/antibiotics10070774
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发表时间：
2021-06-25
期刊：
影响因子：
--
通讯作者：
Nishino K
中科院分区：
文献类型：
--
作者：
Zwama M;Nishino K
多药耐药（MDR）的增加是全球人类健康的最大威胁之一。细菌病原体中的MDR是医疗保健中的主要挑战，因为细菌感染变得无法通过市售抗生素治疗。MDR的主要原因之一是内源性和获得性多药外排泵的过度表达，该泵属于耐药-增殖-分裂（RND）超家族，可外排广泛的结构不同的抗生素。然而，除了过度表达之外，最近在泵本身内的氨基酸替换导致药物外排效率的增加也引起了额外的担忧。在这篇综述中，我们仔细研究了临床，环境和实验室进化的革兰氏阴性细菌菌株及其药物敏感性降低的结果，直接在RND型泵本身的突变（大肠杆菌，沙门氏菌，淋病奈瑟菌，铜绿假单胞菌，鲍曼不动杆菌和嗜肺军团菌）。我们还通过比较数百种外排泵来关注外排泵的演变，以确定保守性集中在哪里，以及氨基酸的差异可以揭示广泛甚至扩大药物识别。知识的保护，以及新的功能获得性外排泵突变，是必不可少的开发新的抗生素和外排泵抑制剂。
The rise in multidrug resistance (MDR) is one of the greatest threats to human health worldwide. MDR in bacterial pathogens is a major challenge in healthcare, as bacterial infections are becoming untreatable by commercially available antibiotics. One of the main causes of MDR is the over-expression of intrinsic and acquired multidrug efflux pumps, belonging to the resistance-nodulation-division (RND) superfamily, which can efflux a wide range of structurally different antibiotics. Besides over-expression, however, recent amino acid substitutions within the pumps themselves—causing an increased drug efflux efficiency—are causing additional worry. In this review, we take a closer look at clinically, environmentally and laboratory-evolved Gram-negative bacterial strains and their decreased drug sensitivity as a result of mutations directly in the RND-type pumps themselves (from Escherichia coli, Salmonella enterica, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Acinetobacter baumannii and Legionella pneumophila). We also focus on the evolution of the efflux pumps by comparing hundreds of efflux pumps to determine where conservation is concentrated and where differences in amino acids can shed light on the broad and even broadening drug recognition. Knowledge of conservation, as well as of novel gain-of-function efflux pump mutations, is essential for the development of novel antibiotics and efflux pump inhibitors.
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影响因子：
3.2
作者：
Bohnert, Juergen A.;Schuster, Sabine;Kern, Winfried V.
通讯作者：
Kern, Winfried V.
影响因子：
5.2
作者：
Dreier J;Ruggerone P
通讯作者：
Ruggerone P
影响因子：
3.7
作者：
Bolla JR;Su CC;Do SV;Radhakrishnan A;Kumar N;Long F;Chou TH;Delmar JA;Lei HT;Rajashankar KR;Shafer WM;Yu EW
通讯作者：
Yu EW
铜绿假单胞菌 TriABC 三氯生排出泵的 "药物清扫 "状态。
DOI：
10.1016/j.str.2020.09.001
发表时间：
2021-03-04
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Fabre L;Ntreh AT;Yazidi A;Leus IV;Weeks JW;Bhattacharyya S;Ruickoldt J;Rouiller I;Zgurskaya HI;Sygusch J
通讯作者：
Sygusch J
影响因子：
7.7
作者：
Eicher, Thomas;Seeger, Markus A.;Pos, Klaas M.
通讯作者：
Pos, Klaas M.