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RNA-seq analysis reveals resistome genes and signalling pathway associated with vancomycin-intermediate Staphylococcus aureus.
Indian Journal of Medical Microbiology ( IF 1.6 ) Pub Date : 2019-01-01 , DOI: 10.4103/ijmm.ijmm_18_311
Devika Subramanian 1 , Jeyakumar Natarajan 1
Affiliation  

Context Vancomycin-intermediate Staphylococcus aureus remains one of the most prevalent multidrug-resistant pathogens causing healthcare infections that are difficult to treat. Aims This study uses a comprehensive computational analysis to systematically investigate various gene expression profiles of resistant and sensitive S. aureus strains on exposure to antibiotics. Settings and Design The transcriptional changes leading to the development of multiple antibiotic resistance were examined by an integrative analysis of nine differential expression experiments under selected conditions of vancomycin-intermediate and -sensitive strains for four different antibiotics using publicly available RNA-Seq datasets. Materials and Methods For each antibiotic, three experimental conditions for expression analysis were selected to identify those genes that are particularly involved in the development of resistance. The results were further scrutinised to generate a resistome that can be analysed for their role in the development or adaptation to antibiotic resistance. Results The 99 genes in the resistome are then compiled to create a multiple drug resistome of 25 known and novel genes identified to play a part in antibiotic resistance. The inclusion of agr genes and associated virulence factors in the identified resistome supports the role of agr quorum sensing system in multiple drug resistance. In addition, enrichment analysis also identified the kyoto encyclopedia of genes and genomes (KEGG) pathways - quorum sensing and two-component system pathways - in the resistome gene set. Conclusion Further studies on understanding the role of the identified molecular targets such as SAA6008_00181, SAA6008_01127, agrA, agrC and coa in adapting to the pressure of antibiotics at sub-inhibitory concentrations can help in learning the molecular mechanisms causing resistance to the pathogens as well as finding other potential therapeutics.

中文翻译:

RNA-seq 分析揭示了与万古霉素中间金黄色葡萄球菌相关的耐药基因和信号通路。

背景 万古霉素中效金黄色葡萄球菌仍然是最常见的多重耐药病原体之一,导致难以治疗的医疗保健感染。目的本研究使用综合计算分析来系统地研究耐药和敏感金黄色葡萄球菌菌株在接触抗生素时的各种基因表达谱。设置和设计使用公开的RNA-Seq数据集,在四种不同抗生素的万古霉素中间和敏感菌株的选定条件下,通过对九个差异表达实验的综合分析来检查导致多种抗生素耐药性发展的转录变化。材料和方法对于每种抗生素,选择三种实验条件进行表达分析,以鉴定那些特别参与耐药性发展的基因。对结果进行进一步审查,以生成抗药性组,可以分析其在抗生素抗性的发展或适应中的作用。结果 然后,对耐药组中的 99 个基因进行编译,创建一个由 25 个已知和新基因组成的多重耐药组,这些基因被确定在抗生素耐药性中发挥作用。已鉴定的抗药性组中包含 agr 基因和相关毒力因子,支持 agr 群体感应系统在多种耐药性中的作用。此外,富集分析还鉴定了抗性基因组中的京都基因和基因组百科全书(KEGG)途径——群体感应和二元系统途径。结论 进一步研究了解已确定的分子靶标(例如 SAA6008_00181、SAA6008_01127、agrA、agrC 和 coa)在适应亚抑制浓度抗生素压力中的作用,有助于了解引起病原体耐药性的分子机制,并有助于了解引起耐药性的分子机制。寻找其他潜在的治疗方法。
更新日期:2019-11-01
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