Iyer Ramkumar, Camilli Andrew
Howard Hughes Medical Institute, Tufts University, Boston, MA 02110, USA.
Mol Microbiol. 2007 Oct;66(1):1-13. doi: 10.1111/j.1365-2958.2007.05878.x.
We characterized two sucrose-metabolizing systems -sus and scr- and describe their roles in the physiology and virulence of Streptococcus pneumoniae in murine models of carriage and pneumonia. The sus and scr systems are regulated by LacI family repressors SusR and ScrR respectively. SusR regulates an adjacent ABC transporter (susT1/susT2/susX) and sucrose-6-phosphate (S-6-P) hydrolase (susH). ScrR controls an adjacent PTS transporter (scrT), fructokinase (scrK) and second S-6-P hydrolase (scrH). sus and scr play niche-specific roles in virulence. The susH and sus locus mutants are attenuated in the lung, but dispensable in nasopharyngeal carriage. Conversely, the scrH and scr locus mutants, while dispensable in the lung, are attenuated for nasopharyngeal colonization. The scrH/susH double mutant is more attenuated than scrH in the nasopharynx, indicating SusH can substitute in this niche. Both systems are sucrose-inducible, with ScrH being the major in vitro hydrolase. The scrH/susH mutant does not grow on sucrose indicating that sus and scr are the only sucrose-metabolizing systems in S. pneumoniae. We propose a model describing hierarchical regulation of the scr and sus systems by the putative inducer, S-6-P. The transport and metabolism of sucrose or a related disaccharide thus contributes to S. pneumoniae colonization and disease.
我们对两种蔗糖代谢系统——sus和scr——进行了表征，并描述了它们在肺炎链球菌于小鼠携带和肺炎模型中的生理学及毒力方面所起的作用。sus和scr系统分别受LacI家族阻遏物SusR和ScrR调控。SusR调控一个相邻的ABC转运蛋白（susT1/susT2/susX）和蔗糖-6-磷酸（S-6-P）水解酶（susH）。ScrR控制一个相邻的磷酸转移酶系统（PTS）转运蛋白（scrT）、果糖激酶（scrK）和第二种S-6-P水解酶（scrH）。sus和scr在毒力方面发挥着特定生态位的作用。susH和sus基因座突变体在肺部的毒力减弱，但在鼻咽部携带中并非必需。相反，scrH和scr基因座突变体虽然在肺部并非必需，但在鼻咽部定殖时毒力减弱。scrH/susH双突变体在鼻咽部比scrH的毒力减弱更明显，表明SusH可以在这个生态位中替代。这两个系统都是蔗糖诱导型的，ScrH是主要的体外水解酶。scrH/susH突变体在蔗糖上无法生长，表明sus和scr是肺炎链球菌中仅有的蔗糖代谢系统。我们提出了一个模型，描述了假定的诱导物S-6-P对scr和sus系统的分级调控。蔗糖或相关二糖的转运和代谢因此有助于肺炎链球菌的定殖和疾病发生。
