Is DNA uptake the Achilles Heel of N. gonorrhoeae?

DNA 摄取是淋病奈瑟菌的致命弱点吗？

• 批准号: 10132982
• 负责人: MAGDALENE Y SO
• 金额: $ 23.81万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132982
• 关键词: Antibiotics; Cells; Competence; DNA; DNA Methylation; Development; Dose; Drug resistance; Formulation; Genes; Genetic; Human; In Vitro; Inbred BALB C Mice; Infection; Light; London; Modeling; Mucous Membrane; Multi-Drug Resistance; Mus; Neisseria; Neisseria elongata; Neisseria gonorrhoeae; Organism; Pathogenicity; Pathway interactions; Resistance; Resistance development; System; Testing; Toxic effect; Universities; Vaccines; Vagina; base; design; irritation; methylation pattern; microbicide; mouse model; mutant; novel; pathogen; prevent; reproductive tract; resistant strain; uptake

Project Summary We recently discovered that commensal Neisseria kill Ngo through a novel mechanism that is based on genetic competence and DNA methylation state. Consistent with these in vitro findings, human commensal N. elongata (Nel) accelerates Ngo clearance from the mouse, and an Ngo DNA uptake mutant resists this clearance. We propose a model for how commensal Neisseria DNA kills Ngo. Based on these and other findings, we hypothesize that any DNA has the potential to kill Ngo, provided it is taken up into the cell and its methylation pattern is considered foreign to the pathogen. In this R21, we propose to this idea using in vitro approaches and the mouse model of Ngo lower genital tract infection. These studies allow us to assess the potential of DNA as an alternative gonococcal microbicide and shed light on a little understood facet of commensal Neisseria-pathogenic Neisseria interactions.

项目总结