Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Friedbühlstrasse 51, CH-3001, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
BMC Microbiol. 2018 Mar 27;18(1):23. doi: 10.1186/s12866-018-1167-y.
Nonencapsulated Streptococcus pneumoniae bacteria are successful colonizers of the human nasopharynx and often possess genes aliB-like ORF 1 and 2 in place of capsule genes. AliB-like ORF 2 binds peptide FPPQSV, found in Prevotella species, resulting in enhanced colonization. How this response is mediated is so far unknown.
Here we show that the peptide increases expression of genes involved in release of host carbohydrates, carbohydrate uptake and carbohydrate metabolism. In particular, the peptide increased expression of 1,5-anhydro-D-fructose reductase, a metabolic enzyme of an alternative starch and glycogen degrading pathway found in many organisms, in both transcriptomic and proteomic data. The peptide enhanced pneumococcal growth giving a competitive advantage to a strain with aliB-like ORF 2, over its mutant lacking the gene. Possession of aliB-like ORF 2 did not affect release of inflammatory cytokine CXCL8 from epithelial cells in culture and the nonencapsulated wild type strain was not able to establish disease or inflammation in an infant rat model of meningitis.
We propose that AliB-like ORF 2 confers an advantage in colonization by enhancing carbohydrate metabolism resulting in a boost in growth. This may explain the widespread presence of aliB-like ORF 2 in the nonencapsulated pneumococcal population in the human nasopharynx.
无荚膜肺炎链球菌是人类鼻咽部的成功定植者,通常具有类似 AliB 的 ORF1 和 2 基因而不是荚膜基因。类似 AliB 的 ORF2 结合肽 FPPQSV,存在于普雷沃氏菌属中,导致增强定植。目前尚不清楚这种反应是如何介导的。
在这里,我们表明该肽增加了参与宿主碳水化合物释放、碳水化合物摄取和碳水化合物代谢的基因的表达。特别是,该肽增加了转录组和蛋白质组数据中 1,5-脱水-D-果糖还原酶的表达,该酶是在许多生物体中发现的替代淀粉和糖原降解途径的代谢酶。该肽增强了肺炎链球菌的生长,使具有类似 AliB 的 ORF2 的菌株相对于缺乏该基因的突变体具有竞争优势。在培养的上皮细胞中,类似 AliB 的 ORF2 的存在并不影响细胞因子 CXCL8 的释放,并且非荚膜野生型菌株不能在婴儿大鼠脑膜炎模型中引起疾病或炎症。
我们提出,类似 AliB 的 ORF2 通过增强碳水化合物代谢来赋予定植优势,从而促进生长。这可能解释了类似 AliB 的 ORF2 在人类鼻咽部无荚膜肺炎链球菌群体中的广泛存在。