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表现出滑动运动，这是一个与粘附宿主细胞（细胞粘附）密不可分的过程，但分子机制尚不确定。此外，不同的系统发育组的支原体似乎粘附和滑行的不同机制。反式支原体是一种主要在HIV阳性患者中发现的生物体，它似乎通过促进HIV感染的细胞类型的增殖来加强AIDS的进展，它也表现出极性形态，并且已知会钻入宿主上皮细胞。然而，其与宿主细胞相互作用的分子基础是完全未知的，其基因组序列表明没有其他生物的细胞粘附蛋白的同源物。我们已经确定了三个不同的M。反式菌株具有滑动运动和粘附性，粘附速度与粘附强度呈正相关。我们已经确定了一个洗涤剂不溶性结构的领导，粘附相关的细胞极和它的两个可能的蛋白质成分。我们将继续通过对洗涤剂不溶性蛋白质的质谱分析以及通过测试相邻基因编码的类似蛋白质是否是组分来鉴定这种细胞极性相关结构的组分。我们将检测极性相关基因的表达，以确定它们是否是共转录的，我们将进一步鉴定M.通过微阵列数据的快速转换，将无菌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M的基因组序列。还没有测序的双反式菌株，并使用比较分析来识别粘附素和马达蛋白的候选基因。这些实验的结果将有助于阐明细胞极性的产生、细胞运动性以及M。因此，我们希望能合理设计这种可能的辅因子的抑制剂。 公共卫生相关性： 虽然对于某些细菌来说，它们是如何移动以及如何附着在它们感染的人的细胞上的，但支原体的行为与其他细菌不同，并且不同类型的支原体的行为彼此不同。反式支原体通常存在于感染艾滋病毒的患者中，导致艾滋病，并被认为导致这些患者的疾病比没有M的个体进展更快。反式感染。在这项研究中，我们将确定与粘附M。M.和M.一般来说，反式脂肪酸会引起疾病。

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.