Two-component regulatory systems in Pseudomonas aeruginosa: an intricate network mediating fimbrial and efflux pump gene expression.

Two-component regulatory systems in Pseudomonas aeruginosa: an intricate network mediating fimbrial and efflux pump gene expression.
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铜绿假单胞菌中的两个组分调节系统:一种复杂的网络,介导纤维化和外排泵基因表达。

DOI:
10.1111/j.1365-2958.2010.07527.x
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发表时间:
2011-03
影响因子:
3.6
通讯作者:
Filloux A
Filloux A
中科院分区:
生物学2区
文献类型:
--
作者:
Sivaneson M;Mikkelsen H;Ventre I;Bordi C;Filloux A

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铜绿假单胞菌是人类慢性和急性感染的原因。慢性感染与菌毛的产生和生物膜的形成有关。双组分系统Roc1因其在杯状基因调控中的作用而命名,杯状基因编码一种允许原毛组装的机制的组成部分。一个未被表征的基因簇roc2编码与Roc1系统同源的成分。我们发现交叉调节发生在Roc1和Roc2信号通路之间。我们证明了传感器RocS2和RocS1会聚在响应调节因子RocA1上以控制cupC基因的表达。这种控制独立于响应调节因子RocA2。相反,我们发现这些传感器通过RocA2反应调节因子来抑制mexAB-oprM基因。这些基因编码一个多药物外排泵,在rocA2突变体中被上调,对抗生素不太敏感。据报道,在囊性纤维化肺中,铜绿假单胞菌采用生物膜生活方式,大多数分离株具有非活性的MexAB-OprM泵。伴随的rocs2依赖性cupC基因(生物膜形成)的上调和mexAB-oprM基因(抗生素耐药性)的下调与这一观察结果一致。这表明Roc系统可能在囊性纤维化肺中感知环境。
Pseudomonas aeruginosa is responsible for chronic and acute infections in humans. Chronic infections are associated with production of fimbriae and the formation of a biofilm. The two-component system Roc1 is named after its role in the regulation of cup genes, which encode components of a machinery allowing assembly of fimbriae. A non-characterized gene cluster, roc2, encodes components homologous to the Roc1 system. We show that cross-regulation occurs between the Roc1 and Roc2 signalling pathways. We demonstrate that the sensors RocS2 and RocS1 converge on the response regulator RocA1 to control cupC gene expression. This control is independent of the response regulator RocA2. Instead, we show that these sensors act via the RocA2 response regulator to repress the mexAB-oprM genes. These genes encode a multidrug efflux pump and are upregulated in the rocA2 mutant, which is less susceptible to antibiotics. It has been reported that in cystic fibrosis lungs, in which P. aeruginosa adopts the biofilm lifestyle, most isolates have an inactive MexAB-OprM pump. The concomitant RocS2-dependent upregulation of cupC genes (biofilm formation) and downregulation of mexAB-oprM genes (antibiotic resistance) is in agreement with this observation. It suggests that the Roc systems may sense the environment in the cystic fibrosis lung.
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发表时间: 1999-01-01
影响因子: 3.6
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