Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients.
Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients.
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DOI：
10.1371/journal.pone.0010115
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发表时间：
2010-04-12
期刊：
影响因子：
3.7
通讯作者：
Scandinavian Cystic Fibrosis Study Consortium
中科院分区：
文献类型：
--
作者：
Bjarnsholt T;Jensen PØ;Jakobsen TH;Phipps R;Nielsen AK;Rybtke MT;Tolker-Nielsen T;Givskov M;Høiby N;Ciofu O;Scandinavian Cystic Fibrosis Study Consortium
铜绿假单胞菌是囊性纤维化患者慢性肺部感染的优势微生物。慢性肺部感染之前是间歇性定植。当慢性感染建立时，分离的菌株与间歇性菌株在表型上不同是公认的。主要的变化是转向粘液性（藻酸盐过量生产）和毒性的表观遗传调节（如群体感应（QS））的丧失。为了阐明铜绿假单胞菌QS系统在CF肺长期感染期间的动力学，我们研究了从152名CF患者中获得的238株分离株，这些患者处于从间歇性到慢性晚期的不同感染阶段。分离的QS信号分子，藻酸盐，鼠李糖脂和弹性蛋白酶的生产和突变频率方面进行了表征。通过对lasR、rhlR、lasI和rhlI基因的序列分析，探讨了QS调节基因改变的遗传基础。第一个丢失的QS系统是在肺部感染发作后12年（中值）由las系统编码的QS系统，随后在17年（中值）后rhl编码系统的丢失分别显示为3-氧代-C12-HSL和C4-HSL QS信号分子产生的缺陷。QS功能障碍的伴随发展与鼠李糖脂和弹性蛋白酶的产生减少以及调节基因lasR和rhlR突变的发生显著相关。lasR和rhlR突变的积累与超变的发展相关。有趣的是，与非粘液分离株相比，发现更多数量的粘液分离株产生C4-HSL信号分子和鼠李糖脂。从目前的数据可以看出，我们可以得出结论，铜绿假单胞菌，特别是粘液菌株不会失去QS调节或产生鼠李糖脂的能力，直到慢性感染的晚期。
Pseudomonas aeruginosa is the predominant microorganism in chronic lung infection of cystic fibrosis patients. The chronic lung infection is preceded by intermittent colonization. When the chronic infection becomes established, it is well accepted that the isolated strains differ phenotypically from the intermittent strains. Dominating changes are the switch to mucoidity (alginate overproduction) and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS). To elucidate the dynamics of P. aeruginosa QS systems during long term infection of the CF lung, we have investigated 238 isolates obtained from 152 CF patients at different stages of infection ranging from intermittent to late chronic. Isolates were characterized with regard to QS signal molecules, alginate, rhamnolipid and elastase production and mutant frequency. The genetic basis for change in QS regulation were investigated and identified by sequence analysis of lasR, rhlR, lasI and rhlI. The first QS system to be lost was the one encoded by las system 12 years (median value) after the onset of the lung infection with subsequent loss of the rhl encoded system after 17 years (median value) shown as deficiencies in production of the 3-oxo-C12-HSL and C4-HSL QS signal molecules respectively. The concomitant development of QS malfunction significantly correlated with the reduced production of rhamnolipids and elastase and with the occurrence of mutations in the regulatory genes lasR and rhlR. Accumulation of mutations in both lasR and rhlR correlated with development of hypermutability. Interestingly, a higher number of mucoid isolates were found to produce C4-HSL signal molecules and rhamnolipids compared to the non-mucoid isolates. As seen from the present data, we can conclude that P. aeruginosa and particularly the mucoid strains do not lose the QS regulation or the ability to produce rhamnolipids until the late stage of the chronic infection.
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影响因子：
3.6
作者：
Diggle, SP;Winzer, K;Williams, P
通讯作者：
Williams, P
DOI：
10.1073/pnas.88.24.11115
发表时间：
1991-12-01
影响因子：
11.1
作者：
CHOI, SH;GREENBERG, EP
通讯作者：
GREENBERG, EP
影响因子：
2.1
作者：
Geisenberger, O;Givskov, M;Eberl, L
通讯作者：
Eberl, L
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：
10
作者：
Kolpen, M.;Hansen, C. R.;Jensen, P. O.
通讯作者：
Jensen, P. O.