The diguanylate cyclase SadC is a central player in Gac/Rsm-mediated biofilm formation in Pseudomonas aeruginosa.
The diguanylate cyclase SadC is a central player in Gac/Rsm-mediated biofilm formation in Pseudomonas aeruginosa.
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DOI：
10.1128/jb.01850-14
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发表时间：
2014-12
影响因子：
3.2
通讯作者：
Filloux A
中科院分区：
文献类型：
--
作者：
Moscoso JA;Jaeger T;Valentini M;Hui K;Jenal U;Filloux A
铜绿假单胞菌是一种革兰氏阴性的机会型人类病原体，对免疫功能低下和囊性纤维化患者构成威胁。它对急性和慢性感染负责，在做出涉及复杂监管网络的知情决定后，可以在这些生活方式之间切换。Rets/lads/Gac/rsm网络和c-di-GMP(c-di-GMP)信号通路都是这种现象的核心，这种现象将铜绿假单胞菌种群重新定向到与慢性感染相关的生物膜生长模式。虽然这两条途径传统上是相互独立研究的，但我们最近发现，在超生物膜rets突变体中，c-di-GMP的细胞水平增加。在这里，我们已经正式建立了两个网络之间的联系，通过证明SADC二鸟苷环化酶是GAC/RSM相关表型的中心，特别是生物膜的形成。重要的是，SADC参与了通过RETS/LAD或HptB/HsbR汇聚到RSMA翻译抑制子上的信号。虽然SADC基因的表达水平似乎没有受到调节级联反应的影响，但SADC蛋白的产生受到RSMA的紧密抑制。这增加了铜绿假单胞菌中与c-di-GMP相关的信号网络的日益复杂。虽然这种生物拥有40多种c-di-GMP相关酶，但仍不清楚c-di-GMP网络中信号特异性是如何维持的。SADC而不是其他的二鸟苷环化酶与GAc/RSM途径控制的生物膜的形成有关，这一发现进一步有助于理解这种绝缘机制。
Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen and a threat for immunocompromised and cystic fibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informed decision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the cyclic-di-GMP (c-di-GMP) signaling pathways are both central to this phenomenon redirecting the P. aeruginosa population toward a biofilm mode of growth, which is associated with chronic infections. While these two pathways were traditionally studied independently from each other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm retS mutant. Here, we have formally established the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsm-associated phenotypes, notably, biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmA translational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the sadC gene does not seem to be impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to the growing complexity of the signaling network associated with c-di-GMP in P. aeruginosa. While this organism possesses more than 40 c-di-GMP-related enzymes, it remains unclear how signaling specificity is maintained within the c-di-GMP network. The finding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway further contributes to understanding of this insulation mechanism.