Nakamya Mary F, Ayoola Moses B, Shack Leslie A, Swiatlo Edwin, Nanduri Bindu
Department of Comparative Biomedical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS 39762, USA.
Section of Infectious Diseases, Southeast Louisiana Veterans Health Care System, New Orleans, LA 70112, USA.
Pathogens. 2021 Oct 14;10(10):1322. doi: 10.3390/pathogens10101322.
Infections due to , a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. Pathogenic mechanisms that allow successful adaption and persistence in the host could be potential innovative therapeutic targets. Polyamines are ubiquitous polycationic molecules that regulate many cellular processes. We previously reported that deletion of polyamine transport operon , which encodes a putrescine/spermidine transporter (Δ), resulted in an unencapsulated attenuated phenotype. Here, we characterize the transcriptome, metabolome, and stress responses of polyamine transport-deficient . Compared with the wild-type strain, the expression of genes involved in oxidative stress responses and the nucleotide sugar metabolism was reduced, while expression of genes involved in the Leloir, tagatose, and pentose phosphate pathways was higher in Δ. A metabolic shift towards the pentose phosphate pathway will limit the synthesis of precursors of capsule polysaccharides. Metabolomics results show reduced levels of glutathione and pyruvate in the mutant. Our results also show that the operon protects pneumococci against hydrogen peroxide and nitrosative stress. Our findings demonstrate the importance of polyamine transport in pneumococcal physiology that could impact in vivo fitness. Thus, polyamine transport in pneumococci represents a novel target for therapeutic interventions.
肺炎链球菌作为鼻咽部的共生菌，其所引发的感染在全球范围内仍导致大量死亡。该病原菌的基因组可塑性、抗生素耐药性以及现有基于多糖的结合疫苗血清型覆盖范围有限，使得限制其传播的治疗干预措施受到困扰。病原体在宿主体内成功适应和持续存在的致病机制可能是潜在的创新治疗靶点。多胺是普遍存在的多阳离子分子，可调节许多细胞过程。我们之前报道过，编码腐胺/亚精胺转运蛋白的多胺转运操纵子（Δ）缺失会导致无荚膜的减毒表型。在此，我们对多胺转运缺陷型肺炎链球菌的转录组、代谢组和应激反应进行了表征。与野生型菌株相比，参与氧化应激反应和核苷酸糖代谢的基因表达降低，而在Δ菌株中，参与Leloir途径、塔格糖途径和磷酸戊糖途径的基因表达较高。向磷酸戊糖途径的代谢转变将限制荚膜多糖前体的合成。代谢组学结果显示突变体中谷胱甘肽和丙酮酸水平降低。我们的结果还表明，操纵子可保护肺炎链球菌免受过氧化氢和亚硝化应激的影响。我们的研究结果证明了多胺转运在肺炎链球菌生理学中的重要性，这可能会影响其体内适应性。因此，肺炎链球菌中的多胺转运代表了治疗干预的新靶点。
