Salmonella promotes virulence by repressing cellulose production
Salmonella promotes virulence by repressing cellulose production
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DOI：
10.1073/pnas.1500989112
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发表时间：
2015-04-21
影响因子：
11.1
通讯作者：
Groisman, Eduardo A.
中科院分区：
文献类型：
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作者：
Pontes, Mauricio H.;Lee, Eun-Jin;Groisman, Eduardo A.
纤维素是地球上含量最丰富的有机聚合物。在细菌中，纤维素提供了对环境侮辱的保护，是通常在非生物表面形成的生物膜的组成部分。我们报告说，令人惊讶的是，肠炎沙门氏菌血清型鼠伤寒沙门氏菌在巨噬细胞内产生纤维素。我们确定，阻止纤维素合成会增加毒力，而刺激巨噬细胞内的纤维素合成会降低毒力。缺乏MGTC基因的弱化突变体由于纤维素合成酶基因BCSA和BCSA蛋白的变构激活剂环二鸟酸酯的表达增加而表现出纤维素水平的增加。灭活BCSA使沙门氏菌MGTC突变体恢复了野生型毒力，但不能恢复其他表现出野生型纤维素表型的减毒突变体。我们的发现表明，毒力决定簇可以通过抑制病原菌的抗毒力特征来促进致病性。此外，他们还提出，控制抗毒力特征可以通过调节急性毒力和传播之间的权衡来提高病原体的长期适合性。
Cellulose is the most abundant organic polymer on Earth. In bacteria, cellulose confers protection against environmental insults and is a constituent of biofilms typically formed on abiotic surfaces. We report that, surprisingly, Salmonella enterica serovar Typhimurium makes cellulose when inside macrophages. We determine that preventing cellulose synthesis increases virulence, whereas stimulation of cellulose synthesis inside macrophages decreases virulence. An attenuated mutant lacking the mgtC gene exhibited increased cellulose levels due to increased expression of the cellulose synthase gene bcsA and of cyclic diguanylate, the allosteric activator of the BcsA protein. Inactivation of bcsA restored wild-type virulence to the Salmonella mgtC mutant, but not to other attenuated mutants displaying a wild-type phenotype regarding cellulose. Our findings indicate that a virulence determinant can promote pathogenicity by repressing a pathogen's antivirulence trait. Moreover, they suggest that controlling antivirulence traits increases long-term pathogen fitness by mediating a trade-off between acute virulence and transmission.