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群体感应系统是一种细胞密度依赖的基因表达系统,其广泛存在于细菌性病原体中,是细菌细胞通讯方式的一种。群体感应系统可利用细菌释放的信号分子不断监控周围细菌的密度。当细菌密度达到阈值时,群体感应系统网络将启动,参与调控生物被膜、细菌毒力等特定基因的表达,从而使临床抗感染治疗失败。而通过抑制群体感应系统,可一定程度上治疗铜绿假单胞菌引起的感染。本文通过查阅近年国内外相关文献,对铜绿假单胞菌群体感应系统研究进展进行总结,为临床铜绿假单胞菌治疗提供新的方向,即群体感应系统抑制剂有可能成为治疗铜绿假单胞菌感染的新策略。 相似文献
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针对调控铜绿假单胞菌致病基因表达的群体感应系统,将相关基因lasI和rhlA的启动子域与蔗糖致死基因相融合,构建出一个能通过菌体生长量来检测群体感应系统小分子抑制物的筛选体系。并在特定条件下,对一系列中药提取物进行筛选,同时用荧光筛选系统对结果进行验证。以此筛选出3种中药提取物对铜绿假单胞菌群体感应系统有不同程度的抑制作用。这3种中药分别隶属于爵床科、败酱科和萝藦科植物。本研究所构建的筛选体系能有效地筛选群体感应系统的抑制物,为进一步了解和控制细菌的致病感染过程和新药物的研究提供了一个有用的工具。 相似文献
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细菌的群体感应也称自身诱导,是指细菌通过产生和感应信号分子浓度的变化来监测其群体密度,协调群体行为的过程.自身诱导物随着细菌密度增高而增高,当自身诱导物达到某一阈值后,会与一些转录调节子结合,从而诱导或抑制多种基因的表达.群体感应系统内由多种信号分子和效应蛋白组成复杂的调节网络,调控包括细菌毒力因子产生与释放、生物膜形成、接合反应等,从而影响细菌的致病过程.本文主要对铜绿假单胞菌的群体感应系统及其与宿主关系、群体感应抑制剂等方面的研究进展进行综述. 相似文献
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铜绿假单胞菌群体感应抑制剂研究进展 总被引:1,自引:0,他引:1
铜绿假单胞菌是一种常见的机会致病菌,可在人群中引起严重的急性和慢性感染,是病人在医院期间发生感染的第三大致病菌。铜绿假单胞菌多种毒力因子的分泌以及生物被膜的形成都是受一种被称为群体感应(Quorum Sensing,QS)的胞间信号传导系统调控的。QS使细菌能够根据细胞密度变化进行基因表达的调控。通过抑制QS来治疗铜绿假单胞菌感染是一个很有前景的发展方向。本文将就近年来铜绿假单胞菌群体感应抑制剂的研究进展进行综述。 相似文献
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A M Albus E C Pesci L J Runyen-Janecky S E West B H Iglewski 《Journal of bacteriology》1997,179(12):3928-3935
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The biochemical network underlying quorum sensing in human-pathogenic Pseudomonas aeruginosa is one of the best characterized. Mathematical modeling is required to untangle the complexity of its architecture and dynamics. We present a qualitative model of the P. aeruginosa quorum-sensing network including interactions between the las and rhl modules, the signaling molecule PQS and the regulatory proteins Mvfr and VfR. Simulations exemplify the model to reproduce natural network behavior and suggest quorum-sensing responses to pharmacological interference. 相似文献
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Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors 总被引:28,自引:0,他引:28
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Hentzer M Wu H Andersen JB Riedel K Rasmussen TB Bagge N Kumar N Schembri MA Song Z Kristoffersen P Manefield M Costerton JW Molin S Eberl L Steinberg P Kjelleberg S Høiby N Givskov M 《The EMBO journal》2003,22(15):3803-3815
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The bacteria Pseudomonas aeruginosa use the size and density of their colonies to regulate the production of a large variety of substances, including toxins.
This phenomenon, called quorum sensing, apparently enables colonies to grow to sufficient size undetected by the immune system
of the host organism.
In this paper, we present a mathematical model of quorum sensing in P. aeruginosa that is based on the known biochemistry of regulation of the autoinducer that is crucial to this signalling mechanism. Using
this model we show that quorum sensing works because of a biochemical switch between two stable steady solutions, one with
low levels of autoinducer and one with high levels of autoinducer. 相似文献
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Megha Shah Véronique L. Taylor Diane Bona Yvonne Tsao Sabrina Y. Stanley Sheila M. Pimentel-Elardo Matthew McCallum Joseph Bondy-Denomy P. Lynne Howell Justin R. Nodwell Alan R. Davidson Trevor F. Moraes Karen L. Maxwell 《Molecular cell》2021,81(3):571-583.e6
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Malladi VL Sobczak AJ Maricic N Murugapiran SK Schneper L Makemson J Mathee K Wnuk SF 《Bioorganic & medicinal chemistry》2011,19(18):5500-5506
Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure γ-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The γ-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations. 相似文献
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Hadas Ganin Xu Tang Michael M. Meijler 《Bioorganic & medicinal chemistry letters》2009,19(14):3941-3944
Autoinducer-2 (AI-2) has been suggested to serve as a universal interspecies quorum sensing signaling molecule. We have synthesized a set of AI-2 analogs with small incremental changes in alkyl substitution on C-2 and evaluated them for their agonistic and antagonistic potential as quorum sensing (QS) attenuators in two different bacterial species: Pseudomonas aeruginosa and Vibrio harveyi. Unexpectedly, several of the analogs were found to function as synergistic QS agonists in V. harveyi, while two of these analogs inhibit QS in P. aeruginosa. 相似文献
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Ishida T Ikeda T Takiguchi N Kuroda A Ohtake H Kato J 《Applied and environmental microbiology》2007,73(10):3183-3188
N-octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhlA-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor, and its concentrations required for half-maximal inhibition for lasB-lacZ and rhlA-lacZ expression were 80 and 90 microM, respectively. C10-CPA also inhibited production of virulence factors, including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-L-homoserine lactone (PAI1) and rhlA-lacZ by N-butanoyl-L-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum-sensing systems via inhibiting interaction between their response regulators (LasR and RhlR) and autoinducers. 相似文献
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生物被膜是一种与浮游细胞相对应的生长方式,由细菌和自身分泌的包外基质组成。铜绿假单胞菌是研究这一生长方式的模式生物。在过去十年,对铜绿假单胞菌生物被膜的研究已取得显著进展。群体感应(QS)的细胞沟通机制在铜绿假单胞菌生物被膜形成中发挥着重要作用。介绍生物被膜的特点,并重点讨论了QS和生物被膜之间的关系。 相似文献
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Lee LY Hupfield T Nicholson RL Hodgkinson JT Su X Thomas GL Salmond GP Welch M Spring DR 《Molecular bioSystems》2008,4(6):505-507
Diastereomeric 2-methoxycyclopentyl analogues of a natural quorum sensing signaling molecule from Pseudomonas aeruginosa were synthesized and screened in pigment production assays with P. aeruginosa and Serratia strain ATCC39006. 相似文献