RND type efflux pump system MexAB-OprM of Pseudomonas aeruginosa selects bacterial languages, 3-oxo-acyl-homoserine lactones, for cell-to-cell communication.
RND type efflux pump system MexAB-OprM of Pseudomonas aeruginosa selects bacterial languages, 3-oxo-acyl-homoserine lactones, for cell-to-cell communication.
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DOI：
10.1186/1471-2180-12-70
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发表时间：
2012-05-10
期刊：
影响因子：
4.2
通讯作者：
Gotoh N
中科院分区：
文献类型：
--
作者：
Minagawa S;Inami H;Kato T;Sawada S;Yasuki T;Miyairi S;Horikawa M;Okuda J;Gotoh N
细菌释放各种各样的小分子，包括细胞间信号化合物。革兰氏阴性菌使用多种自产的自诱导剂，如酰基化同丝氨酸内酯（酰基- hsl）作为细菌物种内部和物种之间群体感应（QS）的信号化合物。QS通过对铜绿假单胞菌中酰基hsl的应答，在感染性疾病的发病机制和有益共生中发挥重要作用。人们认为，细菌语言的选择是调节基因表达所必需的，因此它导致了毒力的调节，并在几种环境中提供了生长优势。在本研究中，我们假设P. aeruginosa的rnd型外排泵系统MexAB-OprM可能在酰基hsl的选择中起作用，并提供证据支持这一假设。由于mexB的缺失，MexAB-OprM的缺失导致了QS应答的增加，lasB启动子下游gfp的表达和lasB弹性酶的活性表明，这是由LasR-3-oxo-C12-HSL复合物调节的。无论是与含有野生型mexB的质粒互补，还是加入lasr特异性抑制剂patulin，都抑制了这些对3-氧酰基hsl的高反应。此外，研究表明，铜绿假单胞菌的酰基hsl依赖性反应受到MexB转运活性抑制和MexB突变体的影响。在细菌串音实验中，铜绿假单胞菌MexAB-OprM缺失突变体对鳗弧菌产生的3-oxo-C10-HSL表现出强烈的QS应答。这项工作表明，在铜绿假单胞菌中，MexAB-OprM并不控制LasR与3-oxo- cn - hsl的结合，而是控制非同源酰基- hsl对LasR的可及性。MexAB-OprM不仅影响P. aeruginosa的多药耐药，还能选择酰基hsl并调节QS。结果证明了铜绿假单胞菌通过外排系统MexAB-OprM调控QS的新机制。
Bacteria release a wide variety of small molecules including cell-to-cell signaling compounds. Gram-negative bacteria use a variety of self-produced autoinducers such as acylated homoserine lactones (acyl-HSLs) as signal compounds for quorum sensing (QS) within and between bacterial species. QS plays a significant role in the pathogenesis of infectious diseases and in beneficial symbiosis by responding to acyl-HSLs in Pseudomonas aeruginosa. It is considered that the selection of bacterial languages is necessary to regulate gene expression and thus it leads to the regulation of virulence and provides a growth advantage in several environments. In this study, we hypothesized that RND-type efflux pump system MexAB-OprM of P. aeruginosa might function in the selection of acyl-HSLs, and we provide evidence to support this hypothesis. Loss of MexAB-OprM due to deletion of mexB caused increases in QS responses, as shown by the expression of gfp located downstream of the lasB promoter and LasB elastase activity, which is regulated by a LasR-3-oxo-C12-HSL complex. Either complementation with a plasmid containing wild-type mexB or the addition of a LasR-specific inhibitor, patulin, repressed these high responses to 3-oxo-acyl-HSLs. Furthermore, it was shown that the acyl-HSLs-dependent response of P. aeruginosa was affected by the inhibition of MexB transport activity and the mexB mutant. The P. aeruginosa MexAB-OprM deletion mutant showed a strong QS response to 3-oxo-C10-HSL produced by Vibrio anguillarum in a bacterial cross-talk experiment. This work demonstrated that MexAB-OprM does not control the binding of LasR to 3-oxo-Cn-HSLs but rather accessibility of non-cognate acyl-HSLs to LasR in P. aeruginosa. MexAB-OprM not only influences multidrug resistance, but also selects acyl-HSLs and regulates QS in P. aeruginosa. The results demonstrate a new QS regulation mechanism via the efflux system MexAB-OprM in P. aeruginosa.
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DOI：
10.1099/00221287-146-10-2469
发表时间：
2000-10-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Laue, RE;Jiang, Y;Williams, P
通讯作者：
Williams, P
影响因子：
2.6
作者：
Hoang, TT;Kutchma, AJ;Schweizer, HP
通讯作者：
Schweizer, HP
影响因子：
4.8
作者：
Bottomley, Matthew J.;Muraglia, Ester;Carfi, Andrea
通讯作者：
Carfi, Andrea
影响因子：
3.5
作者：
Chin-A-Woeng, TFC;van den Broek, D;Bloemberg, GV
通讯作者：
Bloemberg, GV
影响因子：
3.6
作者：
Holden, MTG;Chhabra, SR;Williams, P
通讯作者：
Williams, P