Streptococcus pneumoniae colonizes the human nasopharyngeal mucosa and is a leading cause of community-acquired pneumonia, acute otitis media, and bacterial meningitis. Metal ion homeostasis is vital to the survival of this pathogen across diverse biological sites and contributes significantly to colonization and invasive disease. Microarray and qRT-PCR analysis revealed an upregulation of an uncharacterized operon (SP1433-1438) in pneumococci subjected to metal-chelation by N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN). Supplementation of zinc, cobalt, and nickel following TPEN treatment significantly abrogated induction. BLASTP comparisons and protein topology analysis predicted this locus to encode components of ATP binding cassette (ABC) transporters involved in multidrug resistance (SP1434-1435) and energy-coupling factor (ECF) transporters (SP1436-1438). Inductively coupled plasma mass spectrometry (ICP-MS) analysis identified differences in intracellular metal content in a Δ1434-8 mutant strain compared to parental T4R. Further, analysis of the secreted metabolome of WT and Δ1434-8 strains identified significant changes in pneumococcal glycolytic and amino acid metabolic pathways, indicating a shift towards mixed acid fermentation. Additionally, proteomic analysis revealed differentially expressed proteins in the Δ1434-8 mutant strain, with nearly 20% regulated by the global catabolite repressor, CcpA. Based on these findings, we propose that the transporters encoded by SP1433-1438 are involved in regulating the central metabolism of S. pneumoniae and contributing to bacterial survival during metal stress.

中文翻译：

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肺炎链球菌金属稳态改变细胞代谢。

肺炎链球菌定植于人类鼻咽粘膜，是社区获得性肺炎、急性中耳炎和细菌性脑膜炎的主要原因。金属离子稳态对于这种病原体在不同生物位点的生存至关重要，并且对定植和侵袭性疾病有显着影响。微阵列和 qRT-PCR 分析显示肺炎球菌中一个未表征的操纵子 ( SP1433-1438 ) 被N , N , N ' , N螯合后上调'-四-(2-吡啶基甲基)乙二胺(TPEN)。TPEN 治疗后补充锌、钴和镍可显着消除诱导。BLASTP 比较和蛋白质拓扑分析预测该基因座编码参与多药耐药性 (SP1434-1435) 和能量耦合因子 (ECF) 转运蛋白 (SP1436-1438) 的 ATP 结合盒 (ABC) 转运蛋白的成分。电感耦合等离子体质谱 (ICP-MS) 分析确定了与亲本 T4R 相比，Δ 1434-8突变株中细胞内金属含量的差异。此外，WT和Δ1 434-8的分泌代谢组分析菌株鉴定出肺炎球菌糖酵解和氨基酸代谢途径的显着变化，表明向混合酸发酵的转变。此外，蛋白质组学分析揭示了 Δ 1434-8突变株中差异表达的蛋白质，其中近 20% 受全局分解代谢物阻遏物 CcpA 的调控。基于这些发现，我们提出由SP1433-1438编码的转运蛋白参与调节肺炎链球菌的中枢代谢，并有助于金属应激期间的细菌存活。