Gliding motility and cytadherence in Mycoplasma penetrans

描述(由申请人提供)： 大多数具有极化细胞形态的支原体物种都表现出滑动运动，这一过程与与宿主细胞的黏附(细胞黏附)密不可分，但分子机制不确定。此外，不同的支原体系统发育群似乎通过不同的机制黏附和滑动。穿透性支原体是一种主要在艾滋病毒阳性患者中发现的微生物，它似乎通过促进艾滋病毒感染的细胞类型的增殖来促进艾滋病的进展，也表现出极地形态，并已知可钻入宿主上皮细胞。然而，其与宿主细胞相互作用的分子基础是完全未知的，其基因组序列表明缺乏其他生物的细胞黏附蛋白的同源物。我们已经证实，三种不同的穿透支原体菌株表现出滑动运动和粘附性，粘附性的速度与粘附力呈正相关。我们已经在领先的粘连相关细胞极和它的两个可能的蛋白质组分中确定了一种洗涤剂不溶的结构。我们将继续通过洗涤剂不溶蛋白质的质谱学以及测试相邻基因编码的类似蛋白质是否为成分来识别这种细胞极性相关结构的成分。我们将检测极性相关基因的表达，以确定它们是否共转录，并通过微阵列数据识别进一步的穿透支原体毒力相关基因，将轴向生长的细菌与在宿主细胞存在下生长的细菌进行比较。最后，我们将获得两个尚未测序的穿透支原体菌株的基因组序列，并使用比较分析来确定粘附素和马达蛋白的候选基因。这些实验的结果将阐明细胞极性的产生、细胞的运动性，以及穿透支原体可能导致艾滋病患者疾病的方式，希望合理设计这种可能的辅因子的抑制剂。 公共卫生相关性： 尽管对一些细菌来说，它们是如何移动以及如何附着到它们感染的人的细胞上是众所周知的，但支原体的行为与其他细菌不同，不同类型的支原体的行为也不同。穿透支原体通常在感染艾滋病毒的患者中发现，艾滋病毒会导致艾滋病，据信这些患者的疾病比没有感染穿透支原体的人进展得更快。在这项研究中，我们将确定与穿透支原体与其宿主细胞的黏附、穿透支原体的运动以及一般情况下穿透支原体致病能力相关的分子。

DESCRIPTION (provided by applicant): Most mycoplasma species with polarized cell morphologies exhibit gliding motility, a process inextricably intertwined with adherence to host cells (cytadherence) but of uncertain molecular mechanism. Moreover, different phylogenetic groups of mycoplasmas appear to adhere and glide by different mechanisms. Mycoplasma penetrans, an organism found principally in HIV-positive patients in whom it appears to potentiate the progress of AIDS by promoting proliferation of the type of cell that HIV infects, also exhibits polar morphology and is known to burrow into host epithelial cells. However, the molecular basis for its interaction with host cells is entirely unknown, its genome sequence indicating an absence of homologs of cytadherence proteins of other organisms. We have established that three different M. penetrans strains exhibit gliding motility and adherence with positive correlation between speed and strength of adherence. We have identified a detergent-insoluble structure in the leading, adherence-associated cell pole and two of its probable protein components. We will continue to identify components of this cell polarity-associated structure by mass spectrometry of detergent-insoluble proteins as well as by testing whether similar proteins encoded by adjacent genes are components. We will examine the expression of polarity-associated genes to determine whether they are cotranscribed, and we will identify further virulence-associated genes of M. penetrans through microarray data, comparing bacteria grown axenically with bacteria grown in the presence of host cells. Finally, we will obtain genome sequences for the two M. penetrans strains that are not yet sequenced, and use comparative analysis to identify candidate genes for adhesins and motor proteins. The results of these experiments will shed light on generation of cellular polarity, cellular motility, and the means by which M. penetrans might contribute to the sickness of AIDS patients in hopes of rational design of inhibitors of this likely cofactor. PUBLIC HEALTH RELEVANCE: Although for some bacteria it is understood how they move and how they attach to the cells of people they infect, mycoplasmas behave differently from other bacteria, and different types of mycoplasmas behave differently from one another. Mycoplasma penetrans is usually found in patients infected with HIV, which causes AIDS, and is believed to cause those patients' disease to progress faster than individuals without M. penetrans infection. In this study, we will identify molecules associated with adherence of M. penetrans to the cells of its host, movement of M. penetrans, and the ability of M. penetrans to cause disease in general.