Mycoplasma genitalium Antigenic Variation

生殖支原体是一种新发现的男性尿道炎的病因，可能还会导致宫颈炎症。 妇女中的子宫内膜炎、盆腔炎、非自愿不孕和早产。尽管 在感染期间诱导炎性渗出物和特异性抗体，该有机体持续 在人类中，即使不是几年，也是几个月。我推测这种持久性与生殖支原体的能力有关。 为了躲避其两种表面蛋白--镁蛋白B和镁蛋白C的抗原变异所引起的免疫反应， 位于复合体末端的附着细胞器中。尽管它的基因组极其有限，但 在任何自我复制的细胞有机体中最小的，生殖支原体染色体的4%专门用于部分 两个基因mgpB和mgpC的不完整拷贝，称为mgPars(生殖支原体部分重复序列)。这个 MgpBC表达位点内序列的异质性和与mgPar的同源性？S提示 假设mgpB/mgpC和mgpar位点之间的重组导致抗原变异 产生的mgpB/mgpC蛋白，从而使该有机体能够逃避免疫反应并持续存在。在……里面 初步研究表明，在模式菌株G37体外培养中，mgpB和mgpC是异质性的。 在从持续感染的妇女的宫颈样本中检测到的生殖支原体菌株中。我们也 表明生殖支原体在感染的妇女中诱导宫颈和体液抗体。这些发现提供了 为研究提供了强有力的初步数据：(1)评估 G37中的mgpB、mgpC和mgPar序列，以评估这是否 异质性是由基因转换或相互同源重组产生的，要确定 重组基因的频率及其对体外自发重组的影响；(2)测定 MgpB和MgpC表位的表面暴露和细胞定位，单种生物的生物学活性 针对mgpB和mgpC的抗体以及这些抗体选择抗原变异体的能力 以及(3)鉴定针对特定的mgpB和mgc表位的抗体对 女性持续感染期间mgpB和mgpC变异性的演变。这些研究将导致 对这种受到基因组挑战的有机体所采用的致病机制的更广泛的理解，将 揭示导致抗原变异清除的可能的免疫机制，并将为未来的研究提供信息 评估未来疫苗的可能候选者。

Mycoplasma genitalium is a newly recognized cause of urethritis in men and possibly cervicitis, endometritis, pelvic inflammatory disease, involuntary sterility, and preterm birth in women. Despite the induction of an inflammatory exudate and specific antibodies during infection, this organism persists for months, if not years, in humans. I hypothesize that this persistence is associated with ability of M. genitalium to evade the immune response mediated by antigenic variation in two of its surface proteins, MgpB and MgpC, located in the complex terminally located attachment organelle. Despite its extremely limited genome, the smallest of any self-replicating cellular organism, 4% of the M. genitalium chromosome is devoted to partial incomplete copies of two genes, mgpB and mgpC, termed MgPars (for M. genitalium partial repeats). The sequence heterogeneity within mgpBC expression site and the homology with the MgPar¿s prompted the hypothesis that recombination between mgpB/mgpC and the MgPar sites results in antigenic variation in the resulting MgpB/MgpC proteins, thereby enabling this organism to evade the immune response and persist. In preliminary studies, we show that mgpB and mgpC are heterogeneous in the type strain, G37, cultured in vitro, and among M. genitalium strains detected in cervical specimens from persistently infected women. We also show that M. genitalium induces cervical and humoral antibodies in infected women. These findings provide powerful preliminary data for the studies proposed: (1) to evaluate the heterogeneity and homology of the mgpB, mgpC, and MgPar sequences within G37, the type strain of M. genitalium, to assess whether this heterogeneity is generated by gene conversion or reciprocal homologous recombination, and to determine the frequency, and effect of recombination genes, on spontaneous recombination in vitro; (2) to determine the surface exposure and cellular location of MgpB and MgpC epitopes, the biologic activity of monospecific antibodies directed against MgpB and MgpC, and the ability of these antibodies to select for antigenic variants of these proteins; and (3) to characterize the effect of antibodies to specific MgpB and MgpC epitopes on the evolution of mgpB and mgpC variability during persistent infection in women. These studies will lead to a broader understanding of the pathogenic mechanisms employed by this genomically-challenged organism, will reveal possible immune mechanisms leading to clearance of antigenic variants, and will inform future studies assessing possible candidates for future vaccines.