Nakamya Mary F, Ayoola Moses B, Park Seongbin, Shack Leslie A, Swiatlo Edwin, Nanduri Bindu
Department of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, Mississippi State, MS 39762, USA.
Section of Infectious Diseases, Southeast Louisiana Veterans Health Care System, New Orleans, LA 70112, USA.
Med Sci (Basel). 2018 Jan 19;6(1):8. doi: 10.3390/medsci6010008.
Invasive infections caused by , a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics. Intracellular polyamine concentrations are tightly regulated by biosynthesis, transport and degradation. We previously reported that deletion of a gene that encodes for lysine decarboxylase, an enzyme that catalyzes cadaverine synthesis results in an attenuated phenotype. Here, we report the impact of deletion on pneumococcal capsule and protein expression. Our data show that genes for polyamine biosynthesis and transport are downregulated in . Immunoblot assays show reduced capsule in Reduced capsule synthesis could be due to reduced transcription and availability of precursors for synthesis. The capsule is the predominant virulence factor in pneumococci and is critical for evading opsonophagocytosis and its loss in could explain the reported attenuation in vivo. Results from this study show that capsule synthesis in pneumococci is regulated by polyamine metabolism, which can be targeted for developing novel therapies.
肺炎链球菌是一种寄居于鼻咽部的共生菌，由其引起的侵袭性感染对人类健康构成重大风险。现有的基于多糖的结合疫苗血清型覆盖有限，加之抗生素耐药性的发生率不断上升，使得治疗策略变得复杂。病原体赖以适应宿主的细菌生理学和新陈代谢是发现新型治疗方法的一个有前景的途径。细胞内多胺浓度通过生物合成、转运和降解受到严格调控。我们之前报道，编码赖氨酸脱羧酶（一种催化尸胺合成的酶）的基因缺失会导致肺炎链球菌出现减毒表型。在此，我们报告该基因缺失对肺炎链球菌荚膜和蛋白质表达的影响。我们的数据表明，多胺生物合成和转运相关基因在肺炎链球菌中表达下调。免疫印迹分析显示，该菌的荚膜减少。荚膜合成减少可能是由于转录减少以及合成前体的可利用性降低。荚膜是肺炎链球菌的主要毒力因子，对于逃避调理吞噬作用至关重要，其在该菌中的缺失可以解释所报道的体内减毒现象。本研究结果表明，肺炎链球菌中的荚膜合成受多胺代谢调控，这可为开发新型疗法提供靶点。
