Pontes Mauricio H, Lee Eun-Jin, Choi Jeongjoon, Groisman Eduardo A
Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; Yale Microbial Sciences Institute, West Haven, CT 06516; and.
Howard Hughes Medical Institute and Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; Yale Microbial Sciences Institute, West Haven, CT 06516; and Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Yongin 446-701, Korea.
Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5183-8. doi: 10.1073/pnas.1500989112. Epub 2015 Apr 6.
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.
纤维素是地球上最丰富的有机聚合物。在细菌中，纤维素可抵御环境侵害，是通常在非生物表面形成的生物膜的组成成分。我们报告称，令人惊讶的是，鼠伤寒沙门氏菌在巨噬细胞内时会产生纤维素。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则会降低毒力。一个缺乏mgtC基因的减毒突变体由于纤维素合酶基因bcsA以及BcsA蛋白的变构激活剂环二鸟苷酸的表达增加，从而表现出更高的纤维素水平。使bcsA失活可恢复沙门氏菌mgtC突变体的野生型毒力，但对于在纤维素方面表现出野生型表型的其他减毒突变体则无效。我们的研究结果表明，一种毒力决定因素可通过抑制病原体的抗毒力特性来促进致病性。此外，这些结果表明，通过在急性毒力和传播之间进行权衡，控制抗毒力特性可提高病原体的长期适应性。
