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铜绿假单胞菌 pvdQ 基因对群集条件下改变抗生素敏感性的影响。

Influence of Pseudomonas aeruginosa pvdQ gene on altering antibiotic susceptibility under swarming conditions.

机构信息

Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.

出版信息

Curr Microbiol. 2013 Feb;66(2):152-61. doi: 10.1007/s00284-012-0217-1. Epub 2012 Oct 23.

Abstract

In Pseudomonas aeruginosa PAO1, the pvdQ gene has been shown to have at least two functions. It encodes the acylase enzyme and hydrolyzes 3-oxo-C12-HSL, the key signaling molecule of quorum sensing system. In addition, pvdQ is involved in swarming motility. It is required and up-regulated during swarming motility, which is triggered by high cell densities. As high density bacterial populations also display elevated antibiotics resistance, studies have demonstrated swarm-cell differentiation in P. aeruginosa promotes increased resistance to various antibiotics. PvdQ acts as a signal during swarm-cell differentiation, and thus may play a role in P. aeruginosa antibiotic resistance. The aim of this study was to examine whether pvdQ was involved in modifying antibiotic susceptibility during swarming conditions and to investigate the mechanism by which this occurred. We constructed the PAO1pMEpvdQ strain, which overproduces PvdQ. PAO1pMEpvdQ promotes swarming motility, while PAO1ΔpvdQ abolishes swarming motility. In addition, both PAO1 and PAO1pMEpvdQ acquired resistance to ceftazidime, ciprofloxacin, meropenem, polymyxin B, and gentamicin, though PAO1pMEpvdQ exhibited a twofold to eightfold increase in antibiotic resistance compared to PAO1. These results indicate that pvdQ plays an important role in elevating antibiotic resistance via swarm-cell differentiation and possibly other mechanisms as well. We analyzed outer membrane permeability. Our data also suggest that pvdQ decreases P. aeruginosa outer membrane permeability, thereby elevating antibiotic resistance under swarming conditions. Our results suggest new approaches for reducing P. aeruginosa resistance.

摘要

在铜绿假单胞菌 PAO1 中,pvdQ 基因至少具有两种功能。它编码的酶为酰基酶,可水解 3-氧代-C12-HSL,这是群体感应系统的关键信号分子。此外,pvdQ 还参与群集运动。在由高细胞密度触发的群集运动中,它是必需的并且被上调。由于高密度细菌种群也表现出更高的抗生素耐药性,因此研究表明铜绿假单胞菌中的群集细胞分化促进了对各种抗生素的耐药性增加。PvdQ 在群集细胞分化过程中充当信号,因此可能在铜绿假单胞菌的抗生素耐药性中发挥作用。本研究的目的是检查 pvdQ 是否参与调节群集条件下的抗生素敏感性,并研究发生这种情况的机制。我们构建了过表达 PvdQ 的 PAO1pMEpvdQ 菌株。PAO1pMEpvdQ 促进群集运动,而 PAO1ΔpvdQ 则消除了群集运动。此外,PAO1 和 PAO1pMEpvdQ 对头孢他啶、环丙沙星、美罗培南、多粘菌素 B 和庆大霉素均产生了耐药性,尽管与 PAO1 相比,PAO1pMEpvdQ 对这些抗生素的耐药性提高了 2 到 8 倍。这些结果表明,pvdQ 通过群集细胞分化以及其他可能的机制在提高抗生素耐药性方面发挥着重要作用。我们分析了外膜通透性。我们的数据还表明,pvdQ 降低了铜绿假单胞菌的外膜通透性,从而在群集条件下提高了抗生素的耐药性。我们的结果为降低铜绿假单胞菌耐药性提供了新的方法。

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