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Site-Specific Mutations of GalR Affect Galactose Metabolism in Streptococcus pneumoniae
Journal of Bacteriology ( IF 2.7 ) Pub Date : 2020-12-07 , DOI: 10.1128/jb.00180-20
Kimberley T. McLean 1 , Alexandra Tikhomirova 1 , Erin B. Brazel 1 , Salomé Legendre 1 , Gian Haasbroek 1 , Vikrant Minhas 1 , James C. Paton 1 , Claudia Trappetti 1
Affiliation  

Streptococcus pneumoniae (the pneumococcus) is a formidable human pathogen that is capable of asymptomatically colonizing the nasopharynx. Progression from colonization to invasive disease involves adaptation to distinct host niches, which vary markedly in the availability of key nutrients such as sugars. We previously reported that cell-cell signaling via the autoinducer 2 (AI-2)/LuxS quorum-sensing system boosts the capacity of S. pneumoniae to utilize galactose as a carbon source by upregulation of the Leloir pathway. This resulted in increased capsular polysaccharide production and a hypervirulent phenotype. We hypothesized that this effect was mediated by phosphorylation of GalR, the transcriptional activator of the Leloir pathway. GalR is known to possess three putative phosphorylation sites, S317, T319, and T323. In the present study, derivatives of S. pneumoniae D39 with putative phosphorylation-blocking alanine substitution mutations at each of these GalR sites (singly or in combination) were constructed. Growth assays and transcriptional analyses revealed complex phenotypes for these GalR mutants, with impacts on the regulation of both the Leloir and tagatose 6-phosphate pathways. The alanine substitution mutations significantly reduced the capacity of pneumococci to colonize the nasopharynx, middle ear, and lungs in a murine intranasal challenge model.

中文翻译:

GalR的站点特定突变影响肺炎链球菌中的半乳糖代谢。

肺炎链球菌(肺炎球菌)是一种强大的人类病原体,能够无症状地定居于鼻咽。从定殖到侵袭性疾病的发展涉及对不同宿主生态位的适应,这些关键生态位在关键营养素(如糖)的利用率上有显着差异。我们之前曾报道过通过自动诱导物2(AI-2)/ LuxS群体感应系统进行的细胞间信号传导可增强肺炎链球菌的能力通过上调Leloir途径利用半乳糖作为碳源。这导致荚膜多糖产生增加和超毒表型。我们假设这种作用是由GalR的磷酸化介导的,GalR是Leloir途径的转录激活因子。已知GalR具有三个假定的磷酸化位点,即S317,T319和T323。在本研究中,肺炎链球菌的衍生物构建了在这些GalR位点的每一个(单独或组合)具有假定的磷酸化阻断丙氨酸取代突变的D39。生长测定和转录分析揭示了这些GalR突变体的复杂表型,影响了Leloir和塔格糖6-磷酸途径的调控。在鼠鼻内攻击模型中,丙氨酸替代突变显着降低了肺炎球菌定殖在鼻咽,中耳和肺中的能力。
更新日期:2020-12-07
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