Acinetobacter baumannii Survival under Infection-Associated Stresses Depends on the Expression of Resistance-Nodulation-Division and Major Facilitator Superfamily Efflux Pumps.
Acinetobacter baumannii Survival under Infection-Associated Stresses Depends on the Expression of Resistance-Nodulation-Division and Major Facilitator Superfamily Efflux Pumps.
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DOI：
10.3390/antibiotics13010007
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发表时间：
2023-12-20
影响因子：
4.8
通讯作者：
Zgurskaya, Helen I.
中科院分区：
文献类型：
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作者：
Leus, Inga V.;Olvera, Marcela;Adamiak, Justyna W.;Nguyen, Lauren L.;Zgurskaya, Helen I.
多药外排转运蛋白是临床环境中鲍曼不动杆菌抗生素耐药性的主要贡献者。先前的研究表明，这些转运蛋白与鲍曼不动杆菌的生理学紧密结合，并具有多种功能。然而，对于许多外排泵来说，这些功能仍然没有明确定义。在这项研究中，我们表征了两种假定的药物外排泵 AmfAB 和 AmfCD（不动杆菌主要促进剂），它们与来自大肠杆菌和其他革兰氏阴性细菌的 EmrAB 样转运蛋白同源。这些泵分别包含主要促进子超家族 (MFS) 转运蛋白 AmfB 和 AmfD 以及周质膜融合蛋白 AmfA 和 AmfC。我们在野生型 ATCC 17978 菌株及其衍生菌株中灭活并过量产生这些泵，这些菌株缺乏来自抗性-结瘤-分裂 (RND) 超家族的主要外排泵，并表征了抗生素敏感性和菌株在人类感染期间典型应激下的生长。我们发现 AmfAB 和 AmfCD 都不会导致鲍曼不动杆菌的抗生素不敏感表型。然而，这两个泵对于细菌在酸性胁迫下的适应和生长至关重要，而 AmfCD 也有助于在低铁、高温和胆汁盐存在的条件下生长。这些功能依赖于 RND 泵的存在，RND 泵的失活会进一步降低鲍曼不动杆菌的存活和生长。我们的结果表明，MFS 转运蛋白通过影响鲍曼不动杆菌细胞包膜的渗透性特性来促进应激生存。
Multidrug efflux transporters are major contributors to the antibiotic resistance of Acinetobacter baumannii in clinical settings. Previous studies showed that these transporters are tightly integrated into the physiology of A. baumannii and have diverse functions. However, for many of the efflux pumps, such functions remain poorly defined. In this study, we characterized two putative drug efflux pumps, AmfAB and AmfCD (Acinetobacter Major Facilitator), that are homologous to EmrAB-like transporters from Escherichia coli and other Gram-negative bacteria. These pumps comprise the Major Facilitator Superfamily (MFS) transporters AmfB and AmfD and the periplasmic membrane fusion proteins AmfA and AmfC, respectively. We inactivated and overproduced these pumps in the wild-type ATCC 17978 strain and its derivative strains lacking the major efflux pumps from the Resistance–Nodulation–Division (RND) superfamily and characterized antibiotic susceptibilities and growth of the strains under stresses typical during human infections. We found that neither AmfAB nor AmfCD contribute to the antibiotic non-susceptibility phenotypes of A. baumannii. The two pumps, however, are critical for the adaptation and growth of the bacterium under acidic stress, whereas AmfCD also contributes to growth under conditions of low iron, high temperature, and in the presence of bile salts. These functions are dependent on the presence of the RND pumps, the inactivation of which further diminishes A. baumannii survival and growth. Our results suggest that MFS transporters contribute to stress survival by affecting the permeability properties of the A. baumannii cell envelope.
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DOI：
10.3390/pathogens10030373
发表时间：
2021-03-19
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Kyriakidis I;Vasileiou E;Pana ZD;Tragiannidis A
通讯作者：
Tragiannidis A
影响因子：
4.9
作者：
Krishnamoorthy, Ganesh;Wolloscheck, David;Zgurskaya, Helen I.
通讯作者：
Zgurskaya, Helen I.
影响因子：
3.2
作者：
Leus, Inga, V;Weeks, Jon W.;Zgurskaya, Helen, I
通讯作者：
Zgurskaya, Helen, I
影响因子：
3.4
作者：
Houang, ETS;Sormunen, RT;Leong, ASY
通讯作者：
Leong, ASY
人类细菌病原体的RNA图集发现与感染有关的应力动态。
影响因子：
16.6
作者：
Avican K;Aldahdooh J;Togninalli M;Mahmud AKMF;Tang J;Borgwardt KM;Rhen M;Fällman M
通讯作者：
Fällman M