Meta-Analysis of Human Molecular Responses to Staphylococcus Aureus Components

S. Younis, F. Deeba, S. M. Farhat, Mahwish Ali, Q. Javed, M. Blumenberg
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Abstract

Objective: This study is aimed to identify genes and pathways that are upregulated or downregulated by Staphylococcus aureus components using meta-analysis.Study Design: Meta-analysis of microarray Data.Place and Duration of Study: The study was conducted at R.O. Perelman Department of Dermatology, NYU Langone Medical Center, New York, USA, from January 2015 to March 2015.Materials and Methods: Public repository “GEO Datasets” was searched using key term “Staphylococcus aureus” for data sets covering effects of S. aureus infection in Homo sapiens cells. Meta-analysis was performed using microarray data for immune cell responses to S. aureus components and analyzed using RankProd, RMAExpress, and DAVID software. Results: The secreted factors from biofilm and planktonic cultures predominantly induce adaptive immune process and suppress mitotic cell cycle. The biofilms conditioned media treated keratinocytes upregulate anti-apoptosis genes and immunity while planktonic cultures conditioned media treated keratinocytes upregulate cell cycle as major cytoprotective process. Similar to the secreted factors from S. aureus cultures, superantigens induce adaptive immunity and suppress innate immunity in challenged cells. S. aureus components Panton Valentine Leukocidin (PVL) and iPVL induce adaptive immune system as a defensive mechanism. Importantly, these S. aureus components increased microbicidal activity in host cells. Conclusion: PVL could be a potential priming agent for myeloid cells against virulent S. aureus infections. Further investigations into bactericidal ability of PVL will provide efficient therapy against community-associated Meticillin-resistant Staphylococcus aureus (CA-MRSA) infections.
人类对金黄色葡萄球菌成分分子反应的荟萃分析
目的:本研究旨在通过荟萃分析确定金黄色葡萄球菌成分上调或下调的基因和途径。研究设计:微阵列数据的荟萃分析。研究地点和时间:研究于2015年1月至2015年3月在美国纽约大学朗格尼医学中心R.O. Perelman皮肤科进行。材料与方法:检索公共数据库“GEO Datasets”,关键词为“Staphylococcus aureus”,检索涵盖金黄色葡萄球菌感染智人细胞效应的数据集。使用微阵列数据对免疫细胞对金黄色葡萄球菌成分的反应进行meta分析,并使用RankProd、RMAExpress和DAVID软件进行分析。结果:生物膜和浮游培养的分泌因子主要诱导适应性免疫过程,抑制有丝分裂细胞周期。生物膜条件培养基上调角质形成细胞的抗凋亡基因和免疫,而浮游培养条件培养基上调角质形成细胞的细胞周期作为主要的细胞保护过程。与金黄色葡萄球菌培养物的分泌因子类似,超抗原在受激细胞中诱导适应性免疫并抑制先天免疫。金黄色葡萄球菌成分Panton Valentine Leukocidin (PVL)和iPVL诱导适应性免疫系统作为防御机制。重要的是,这些金黄色葡萄球菌成分增加了宿主细胞中的杀微生物活性。结论:PVL可能是骨髓细胞抗金黄色葡萄球菌感染的潜在引物。PVL杀菌能力的进一步研究将为对抗社区相关的耐甲氧西林金黄色葡萄球菌(CA-MRSA)感染提供有效的治疗方法。
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