Cyclic di-GMP stimulates biofilm formation and inhibits virulence of Francisella novicida.
Cyclic di-GMP stimulates biofilm formation and inhibits virulence of Francisella novicida.
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环状二-GMP 刺激生物膜形成并抑制新杀弗朗西斯菌的毒力。
DOI：
10.1128/iai.00702-12
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发表时间：
2012
影响因子：
3.1
通讯作者：
Klose,KarlE
中科院分区：
文献类型：
--
作者：
Zogaj,Xhavit;Wyatt,GeoffC;Klose,KarlE
土拉热弗朗西丝菌是一种革兰氏阴性细菌，在人类中具有高度毒性，导致土拉菌病。F. novicida与F.土拉热，并在小鼠中表现出高毒力，但在健康人体中无毒力。一个F。novicida特异性基因簇（FTN 0451至FTN 0456）编码具有二鸟苷酸环化酶（DGC）和磷酸二酯酶（PDE）结构域的两种蛋白质，其调节环二GMP（cdGMP）的合成和降解。在F.土拉热菌基因组。F.缺乏两个DGC/PDE基因（cdgA和cdgB）或整个基因簇（菌株KKF 457）的杀线虫菌株对于生物膜形成是有缺陷的。此外，CdgB或异源DGC在菌株KKF 457中的表达刺激了F.杀线虫生物膜，即使在缺乏生物膜调节剂QseB的菌株中。遗传证据表明，CdgA主要是PDE，而CdgB主要是DGC。F。novicida qseB菌株cdgA和cdgB转录水平降低，表明F.杀线虫生物膜信号级联，控制cdGMP水平。有趣的是，cdGMP水平升高的KKF 457在小鼠中表现出巨噬细胞内复制和毒力的降低，以及体外生长产量和生物膜形成的增加。微阵列分析显示，cdGMP刺激已知有助于生物膜形成的几丁质酶（ChiB）的转录。我们的研究结果表明，在F.杀线虫剂刺激生物膜形成并抑制毒力。我们认为F. novicida和F.土拉热可能部分是由于F.土拉热。
Francisella tularensis is a Gram-negative bacterium that is highly virulent in humans, causing the disease tularemia. F. novicida is closely related to F. tularensis and exhibits high virulence in mice, but it is avirulent in healthy humans. An F. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE-encoding protein genes are present in the F. tularensis genome. F. novicida strains lacking either the two DGC/PDE genes (cdgAandcdgB) or the entire gene cluster (strain KKF457) are defective for biofilm formation. In addition, expression of CdgB or a heterologous DGC in strain KKF457 stimulated F. novicida biofilms, even in a strain lacking the biofilm regulator QseB. Genetic evidence suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC. TheF. novicida qseBstrain showed reducedcdgAandcdgBtranscript levels, demonstrating an F. novicida biofilm signaling cascade that controls cdGMP levels. Interestingly, KKF457 with elevated cdGMP levels exhibited a decrease in intramacrophage replication and virulence in mice, as well as increased growth yields and biofilm formationin vitro. Microarray analyses revealed that cdGMP stimulated the transcription of a chitinase (ChiB) known to contribute to biofilm formation. Our results indicate that elevated cdGMP in F. novicida stimulates biofilm formation and inhibits virulence. We suggest that differences in human virulence between F. novicida and F. tularensis may be due in part to the absence of cdGMP signaling in F. tularensis.