Mass spectrometry-based proteomics and its application to studies of Porphyromonas gingivalis invasion and pathogenicity
Mass spectrometry-based proteomics and its application to studies of Porphyromonas gingivalis invasion and pathogenicity
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DOI：
10.2174/187152606778249935
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发表时间：
2006-09-01
影响因子：
--
通讯作者：
Hackett, Murray
中科院分区：
文献类型：
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作者：
Lamont, Richard J.;Meila, Marina;Hackett, Murray
牙龈卟啉单胞菌（Porphyromonas gingivalis）是一种革兰氏阴性厌氧菌，存在于口腔的龈下缝隙中。已知它经历从健康个体中的细胞内状态到患有牙周病的人类患者中的高度侵入性细胞内病原体的转变，在那里它通常是致病细菌的优势物种。本文综述了基于质谱的蛋白质组学在牙龈卟啉单胞菌与模式宿主细胞系统相互作用、侵袭和致病性研究中的应用。这些研究已经从使用传统的基于凝胶的方法对少量分泌蛋白质进行定性鉴定发展到使用多维毛细管HPLC与线性离子阱质谱联用的定量全细胞蛋白质组学研究。以类似于全基因组mRNA阵列的方式，在整个牙龈卟啉单胞菌蛋白质组上产生蛋白质表达变化的差异读数已经成为可能。已经采用不同的策略来从质谱数据生成蛋白质水平表达比率，包括稳定同位素代谢标记和最近的光谱计数方法。由于现有的数据库搜索和数据挖掘计算工具的限制，蛋白质修饰状态变化的全局视图仍然难以捉摸。这样的观点将是可取的目的，使全球评估的变化，在响应宿主的相互作用过程中的粘附，入侵和内化的基因调控。有了一个完整的数据矩阵，包括在入侵过程中的转录，蛋白质丰度和蛋白质修饰的变化，寻找新的蛋白质药物靶标将受益于对这些过程的更全面的理解，而不是在系统生物学出现之前所能实现的。
Porphyromonas gingivalis is a Gram-negative anaerobe that populates the subgingival crevice of the mouth. It is known to undergo a transition from its commensal status in healthy individuals to a highly invasive intracellular pathogen in human patients suffering from periodontal disease, where it is often the dominant species of pathogenic bacteria. The application of mass spectrometry-based proteomics to the study of P. gingivalis interactions with model host cell systems, invasion and pathogenicity is reviewed. These studies have evolved from qualitative identifications of small numbers of secreted proteins, using traditional gel-based methods, to quantitative whole cell proteomic studies using multiple dimension capillary HPLC coupled with linear ion trap mass spectrometry. It has become possible to generate a differential readout of protein expression change over the entire P. gingivalis proteome, in a manner analogous to whole genome mRNA arrays. Different strategies have been employed for generating protein level expression ratios from mass spectrometry data, including stable isotope metabolic labeling and most recently, spectral counting methods. A global view of changes in protein modification status remains elusive due to the limitations of existing computational tools for database searching and data mining. Such a view would be desirable for purposes of making global assessments of changes in gene regulation in response to host interactions during the course of adhesion, invasion and internalization. With a complete data-matrix consisting of changes in transcription, protein abundance and protein modification during the course of invasion, the search for new protein drug targets would benefit from a, more comprehensive understanding of these processes than what could be achieved prior to the advent of systems biology.