Toward implementation of quorum sensing autoinducers as biomarkers for infectious disease states.
Toward implementation of quorum sensing autoinducers as biomarkers for infectious disease states.
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DOI：
10.1021/ac400032a
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发表时间：
2013-03-19
影响因子：
7.4
通讯作者：
Janda, Kim D.
中科院分区：
文献类型：
--
作者：
Struss, Anjali K.;Nunes, Ashlee;Waalen, Jill;Lowery, Colin A.;Pullanikat, Prasanna;Denery, Judith R.;Conrad, Douglas J.;Kaufmann, Gunnar F.;Janda, Kim D.
条件致病菌铜绿假单胞菌可引起囊性纤维化(CF)患者的慢性肺部感染。重要的是，在铜绿假单胞菌中，毒力因子的表达和生物膜的形成是通过群体感应(QS)来协调的，其中一个关键的QS信号分子是3-oxo-C12-HSL。值得注意的是，在生理条件下，3-氧代-C12-HSL自发生成具有抗菌性能的四酸(C12-TA)。为了更好地了解这种关系，我们试图研究3-oxo-C12-HSL和C12-TA是否可能是CF患者铜绿假单胞菌整体致病性的贡献因素，以及它们在痰标本中的检测和定量可能作为评估CF患者病情和监测治疗成功的指标。为此，采用液-质联用技术初步分析了铜绿假单胞菌Flow细胞生物膜中3-oxo-C12-HSL和C12-TA的浓度。建立了一种基于LC-MS-MS的方法，并验证了其在CF患者痰中的检测和定量。我们强调，这是第一个显示在人类临床样本(如痰)中同时存在群体感应分子(3-oxo-C12-HSL)及其重排产物(C12-TA)的报告。对20例慢性肺囊炎患者和2例非慢性肺囊炎患者的47份痰标本进行了分析：45份标本中检测到3-oxo-C12-HSL，浓度范围为20~1000 nm；14份标本中检出C12-TA(13~900 nm)。根据我们的发现，群体感应自身诱导物作为传染病状态的生物标志物值得进一步研究。
The opportunistic bacterial pathogen Pseudomonas aeruginosa causes chronic lung infections in cystic fibrosis (CF) patients. Importantly, virulence factor expression and biofilm formation in P. aeruginosa is coordinated by quorum sensing (QS) and one of the key QS signaling molecules is 3-oxo-C12-HSL. Remarkably, a tetramic acid, (C12-TA), with antibacterial properties is formed spontaneously from 3-oxo-C12-HSL under physiological conditions. Seeking to better understand this relationship we sought to investigate if 3-oxo-C12-HSL and C12-TA may be contributing factors to the overall pathogenicity of P. aeruginosa in CF individuals and their detection and quantitation in sputum samples might be used as an indicator to assess disease states and monitor therapy success in CF patients. To this end, 3-oxo-C12-HSL and C12-TA concentrations were initially analyzed in P. aeruginosa flow cell biofilms using liquid chromatography coupled with mass spectrometry (LC-MS). A liquid chromatography tandem mass spectrometry (LC-MS-MS)-based method was then developed and validated for their detection and quantification in sputa of CF patients. We highlight that this is the first report to show the presence of both the quorum sensing molecule (3-oxo-C12-HSL) and its rearranged product (C12-TA) in human clinical samples such as sputum. A total of 47 sputum samples from 20 CF and 2 non-CF individuals were analyzed: 3-oxo-C12-HSL was detected and quantified in 45 samples with concentrations ranging from 20 nM to >1000 nM; C12-TA was found in 14 samples (13 – 900 nM). Based on our findings, quorum sensing autoinducers merit further investigation as biomarkers for infectious disease states.
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定义源自铜绿假单胞菌群体传感信号的四酸抗菌物的作用方式。
影响因子：
15
作者：
Lowery, Colin A.;Park, Junguk;Gloeckner, Christian;Meijler, Michael M.;Mueller, Ryan S.;Boshoff, Helena I.;Ulrich, Ricky L.;Barry, Clifton E., III;Bartlett, Douglas H.;Kravchenko, Vladimir V.;Kaufmann, Gunnar F.;Janda, Kim D.
通讯作者：
Janda, Kim D.
影响因子：
56.9
作者：
Kravchenko, Vladimir V.;Kaufmann, Gunnar F.;Ulevitch, Richard J.
通讯作者：
Ulevitch, Richard J.
影响因子：
3.1
作者：
Erickson, DL;Endersby, R;Storey, DG
通讯作者：
Storey, DG
影响因子：
5.1
作者：
Charlton, TS;de Nys, R;Kjelleberg, S
通讯作者：
Kjelleberg, S
影响因子：
9.3
作者：
Høiby N
通讯作者：
Høiby N