Role of host cell invasion in Mycoplasma genitalium persistent infection

 描述(申请人提供)：生殖支原体(MG)是一种新出现的性传播病原体，可导致男性非淋球菌性尿道炎，并与女性的一系列生殖道疾病密切相关。在临床上，根除MG仍然是一项艰巨的任务，治疗失败率高表明MG可以导致持续感染。目前还不清楚MG如何在宿主生殖道中持续存在。虽然长期以来一直认为抗原变异是导致MG持续感染的原因，但这一机制不能解释标准抗生素治疗后MG持续感染的原因。我们的研究表明，MG在体外和体内都具有侵袭宿主细胞的能力，细胞内的MG可以在一定的抗生素和完整的免疫系统存在下长期存活。这些发现使我们假设MG对宿主细胞的入侵是持续感染所必需的。在我们成功获得细胞侵袭能力不足但具有完整细胞黏附能力的MG突变体的基础上，本研究旨在深入了解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的持续存在和发病机制是否需要MG的侵袭。这些研究将证实MG的侵袭和细胞内定位在持续感染和发病机制中的作用。所获得的知识将为进一步剖析MG-宿主相互作用和改善MG感染的临床管理奠定基础。

 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.