Exposure of Salmonella enterica Serovar Typhimurium to a Protective Monoclonal IgA Triggers Exopolysaccharide Production via a Diguanylate Cyclase-Dependent Pathway
Exposure of Salmonella enterica Serovar Typhimurium to a Protective Monoclonal IgA Triggers Exopolysaccharide Production via a Diguanylate Cyclase-Dependent Pathway
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DOI：
10.1128/iai.00813-12
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发表时间：
2013-03-01
影响因子：
3.1
通讯作者：
Mantis, Nicholas J.
中科院分区：
文献类型：
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作者：
Amarasinghe, Jayaleka J.;D'Hondt, Rebecca E.;Mantis, Nicholas J.
Sal 4是针对沙门氏菌血清型鼠伤寒沙门氏菌（S.鼠伤寒沙门氏菌），这足以保护小鼠免受肠道感染的S。鼠伤寒我们最近报道了S.鼠伤寒沙门氏菌Sal 4的结果在鞭毛为基础的运动性的立即损失，在改变外膜（OM）的完整性，并在一个粘液样表型，这是在生物膜形成的最早阶段的细胞联想到伴随的外观。我们在这里证明，延长（>4小时）暴露的S。鼠伤寒沙门氏菌在37 ℃下（但不是在环境温度[25 ℃]下）转化为Sal 4导致硼硅酸盐玻璃表面和聚苯乙烯微量滴定板上可测量的外多糖（EPS）积累和生物膜形成。S.鼠伤寒沙门氏菌对Sal 4有反应，除O-Ag荚膜和可拉酸外，还含有纤维素。EPS生产依赖于YeaJ，一种提议的内膜定位的二鸟苷酸环化酶（DGC）和纤维素生物合成的已知调节剂。色葡萄鼠伤寒沙门氏菌Delta yeaJ菌株不能产生纤维素或形成生物膜响应Sal 4。相反，在S.与野生型对照相比，鼠伤寒沙门氏菌增强了Sal 4诱导的生物膜形成，并导致细胞内环状二聚鸟苷一磷酸（c-di-GMP）水平增加;这强烈表明YeaJ确实是一种功能性DGC。基于这些数据，我们推测Sal 4，凭借其与O-Ag结合并诱导OM应力的能力，使S.通过YeaJ触发c-di-GMP依赖性信号传导途径，导致细菌运动性抑制，同时刺激EPS产生，使鼠伤寒沙门氏菌无毒。
Sal4 is a monoclonal polymeric IgA antibody directed against the O antigen (O-Ag) of Salmonella enterica serovar Typhimurium (S. Typhimurium), which is sufficient to protect mice against intestinal infections from S. Typhimurium. We recently reported that the exposure of S. Typhimurium to Sal4 results in the immediate loss of flagellum-based motility, in alterations to the outer membrane (OM) integrity, and in the concomitant appearance of a mucoid phenotype that is reminiscent of cells in the earliest stages of biofilm formation. We demonstrate here that prolonged (>4 h) exposure of S. Typhimurium to Sal4 at 37 degrees C (but not at ambient temperature [25 degrees C]) results in measurable exopolysaccharide (EPS) accumulation and biofilm formation on both boro-silicate glass surfaces and polystyrene microtiter plates. The polysaccharide produced by S. Typhimurium in response to Sal4 contains cellulose, in addition to O-Ag capsule and colanic acid. EPS production was dependent on YeaJ, a proposed inner membrane-localized diguanylate cyclase (DGC) and a known regulator of cellulose biosynthesis. An S. Typhimurium Delta yeaJ strain was unable to produce cellulose or form a biofilm in response to Sal4. Conversely, the overexpression of yeaJ in S. Typhimurium enhanced Sal4-induced biofilm formation and resulted in increased intracellular levels of cyclic dimeric guanosine monophosphate (c-di-GMP) compared to that of a wild-type control; this strongly suggests that YeaJ is indeed a functional DGC. Based on these data, we speculate that Sal4, by virtue of its ability to associate with the O-Ag and to induce OM stress, renders S. Typhimurium avirulent by triggering a c-di-GMP-dependent signaling pathway via YeaJ that leads to the suppression of bacterial motility while simultaneously stimulating EPS production.