Role of host cell invasion in Mycoplasma genitalium persistent infection

宿主细胞侵袭在生殖支原体持续感染中的作用

• 批准号: 9197256
• 负责人: JOEL Barry BASEMAN
• 金额: $ 19.06万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-17 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197256
• 关键词: Animal Model; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antigenic Variation; Biochemical; Biological Assay; Cell Culture Techniques; Cells; Chronic; Clinical; Clinical Management; Complement; Development; Disease; Evaluation; Gene Targeting; Genes; Genetic; Genitourinary system; Genome; Goals; Health; High Prevalence; Histologic; Immune response; Immune system; Immunity; Immunize; Immunologics; In Vitro; Infection; Invaded; Knowledge; Laboratories; Latex Bead; Lead; Libraries; Mammalian Cell; Mediating; Modality; Modeling; Molecular; Monitor; Mus; Mycoplasma genitalium; Nonspecific urethritis; Pathogenesis; Pathology; Public Health; Recombinants; Regimen; Reporting; Role; Sexually Transmitted Diseases; Testing; Therapeutic Intervention; Time; Tissues; Treatment Failure; Woman; base; experimental study; genome-wide; improved; in vivo; innovation; insight; men; mutant; pathogen; polyclonal antibody; public health relevance; reproductive tract; residence; success; transmission process; virtual; whole genome; young adult

 DESCRIPTION (provided by applicant): Mycoplasma genitalium (MG) is an emerging sexually transmitted pathogen that causes non-gonococcal urethritis in men and has been significantly associated with a range of reproductive tract diseases in women. Clinically, MG eradication remains a difficult task, and high rates of treatment failure indicate MG can cause persistent infection. It is unclear how MG persists in the host genital tract. Although antigenic variation has long been believed to contribute to MG persistence, this mechanism fails to explain MG persistent infection following standard antibiotic treatment. Our studies indicate that MG is capable of host cell invasion in vitro and in vivo and that intracellular MG can survive long-term in the presence of certain antibiotics and intact immune system. These findings have led us to hypothesize that MG invasion of host cells is required for persistent infection. On the basis of our success of obtaining MG mutants that are deficient in cell invasion but retain intact cytadherence capabilities, this proposal is aimed to gain insight into the mechanisms of MG persistent infection. We propose to (1) identify MG genes required for host cell invasion; and (2) determine whether MG invasion is required for MG persistence and pathogenesis. The proposed studies will substantiate the role of MG invasion and intracellular localization in persistent infection and pathogenesis. Knowledge obtained will set the stage for further dissecting MG-host interactions and improving clinical management of MG infection.

 描述（由适用提供）：支原体生殖器（MG）是一种新兴的性传播病原体，可导致男性非癌症肠炎，并且与女性的一系列生殖道疾病显着相关。在临床上，消除MG仍然是一项艰巨的任务，高治疗失败的率表明MG会导致持续感染。目前尚不清楚MG在宿主生殖道中如何持续。尽管长期以来一直认为抗原性变异会导致MG持久性，但该机制无法解释标准抗生素治疗后MG持续感染。我们的研究表明，MG能够在体外和体内宿主细胞侵袭，并且在某些抗生素和完整的免疫系统的情况下，细胞内MG可以长期生存。这些发现使我们假设MG侵入宿主细胞是持续感染所必需的。基于我们成功获得细胞侵袭但保留完整的CytaDherence功能的MG突变体，该建议旨在深入了解MG持续感染的机制。我们建议（1）确定宿主细胞侵袭所需的Mg基因； （2）确定MG持久性和发病机理是否需要Mg侵袭。拟议的研究将证实MG侵袭和细胞内定位在持续感染和发病机理中的作用。获得的知识将为进一步剖析MG-host相互作用并改善MG感染的临床管理奠定基础。