Department of Biosciences and Biomedical Engineering, Indian Institute of Technology, Simrol, Indore 453552, India.
ACS Infect Dis. 2022 Apr 8;8(4):728-743. doi: 10.1021/acsinfecdis.1c00383. Epub 2022 Mar 4.
The noncanonical structures, G-quadruplexes (GQs), formed in the guanine-rich region of nucleic acids regulate various biological and molecular functions in prokaryotes and eukaryotes. is a commensal residing in a human's upper respiratory tract but occasionally becomes virulent, causing life-threatening septicemia and meningitis. The factors causing these changes in phenotypes are not fully understood. At the molecular level, regulatory components help in a clearer understanding of the pathogen's virulence and pathogenesis. Herein, genome analysis followed by biophysical assays and cell-based experiments revealed the presence of conserved GQ motifs in . These GQs are linked to the essential genes involved in cell adhesion, pathogenesis, virulence, transport, DNA repair, and recombination. Primer extension stop assay, reporter assays, and quantitative real-time polymerase chain reaction (qRT-PCR) further affirmed the formation of stable GQs and . These results support the existence of evolutionarily conserved GQ motifs in and uphold the usage of GQ-specific ligands as novel antimeningococcal therapeutics.
非canonical 结构,G-四链体(GQs),在富含鸟嘌呤的核酸区域形成,调节原核生物和真核生物中的各种生物和分子功能。 是一种居住在上呼吸道的共生菌,但偶尔会变得有毒,导致危及生命的败血症和脑膜炎。导致这些表型变化的因素尚不完全清楚。在分子水平上,调控成分有助于更清楚地了解病原体的毒力和发病机制。在此,通过基因组分析,结合生物物理测定和基于细胞的实验,揭示了 中存在保守的 GQ 基序。这些 GQs 与参与细胞黏附、发病机制、毒力、运输、DNA 修复和重组的必需基因有关。引物延伸停止测定、报告基因测定和实时定量聚合酶链反应(qRT-PCR)进一步证实了稳定 GQs 的形成 和 。这些结果支持 中存在进化保守的 GQ 基序,并支持使用 GQ 特异性配体作为新型抗脑膜炎球菌治疗药物。