Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Mol Microbiol. 2012 Apr;84(2):296-309. doi: 10.1111/j.1365-2958.2012.08022.x. Epub 2012 Mar 9.
Mechanisms by which Salmonella establish chronic infections are not well understood. Microbes respond to stress by importing or producing compatible solutes, small molecules that stabilize proteins and lipids. The Salmonella locus opuABCD (also called OpuC) encodes a predicted importer of the compatible solute glycine betaine. Under stress conditions, if glycine betaine cannot be imported, Salmonella enterica produce the disaccharide trehalose, a highly effective compatible solute. We demonstrate that strains lacking opuABCD accumulate more trehalose under stress conditions than wild-type strains. ΔopuABCD mutant strains are more resistant to high-salt, low-pH and -hydrogen peroxide, conditions that mimic aspects of innate immunity, in a trehalose-dependent manner. In addition, ΔopuABCD mutant strains require the trehalose production genes to out-compete wild-type strains in mice and macrophages. These data suggest that in the absence of opuABCD, trehalose accumulation increases bacterial resistance to stress in broth and mice. Thus, opuABCD reduces bacterial colonization via a mechanism that limits trehalose production. Mechanisms by which microbes limit disease may reveal novel pathways as therapeutic targets.
沙门氏菌建立慢性感染的机制尚不清楚。微生物通过导入或产生相容溶质（稳定蛋白质和脂质的小分子）来应对压力。沙门氏菌的 opuABCD 基因座（也称为 OpuC）编码一种预测的相容溶质甘氨酸甜菜碱的导入器。在应激条件下，如果不能导入甘氨酸甜菜碱，沙门氏菌就会产生二糖海藻糖，这是一种非常有效的相容溶质。我们证明，缺乏 opuABCD 的菌株在应激条件下积累的海藻糖比野生型菌株多。ΔopuABCD 突变株在高盐、低 pH 和 -过氧化氢条件下（这些条件模拟了先天免疫的某些方面）比野生型菌株更具抗性，这种抗性依赖于海藻糖。此外，ΔopuABCD 突变株需要海藻糖产生基因才能在小鼠和巨噬细胞中与野生型菌株竞争。这些数据表明，在缺乏 opuABCD 的情况下，海藻糖的积累增加了细菌在肉汤和小鼠中的抗应激能力。因此，opuABCD 通过限制海藻糖产生的机制降低了细菌的定植能力。微生物限制疾病的机制可能揭示出作为治疗靶点的新途径。
