Gene regulatory network inference and analysis of multidrug-resistant Pseudomonas aeruginosa

BACKGROUND Healthcare-associated infections caused by bacteria such as Pseudomonas aeruginosa are a major public health problem worldwide. Gene regulatory networks (GRN) computationally represent interactions among regulatory genes and their targets. They are an important approach to help understand bacterial behaviour and to provide novel ways of overcoming scientific challenges, including the identification of potential therapeutic targets and the development of new drugs. OBJECTIVES The goal of this study was to reconstruct the multidrug-resistant (MDR) P. aeruginosa GRN and to analyse its topological properties. METHODS The methodology used in this study was based on gene orthology inference using the reciprocal best hit method. We used the genome of P. aeruginosa CCBH4851 as the basis of the reconstruction process. This MDR strain is representative of the sequence type 277, which was involved in an endemic outbreak in Brazil. FINDINGS We obtained a network with a larger number of regulatory genes, target genes and interactions as compared to the previously reported network. Topological analysis results are in accordance with the complex network representation of biological processes. MAIN CONCLUSIONS The properties of the network were consistent with the biological features of P. aeruginosa. To the best of our knowledge, the P. aeruginosa GRN presented here is the most complete version available to date.背景 由铜绿假单胞菌（Pseudomonas aeruginosa）等细菌引发的医院获得性感染，是全球范围内的重大公共卫生问题。基因调控网络（Gene Regulatory Networks, GRN）通过计算方式表征调控基因与其靶基因之间的相互作用，是助力解析细菌行为、攻克科学难题的重要手段，涵盖潜在治疗靶点筛选与新型药物研发等研究方向。 目的 本研究旨在重建多重耐药（multidrug-resistant, MDR）铜绿假单胞菌的基因调控网络，并分析其拓扑属性。 方法 本研究采用基于双向最佳匹配法的基因直系同源推断策略，以铜绿假单胞菌CCBH4851的基因组作为网络重建的基础。该多重耐药菌株属于序列型277（ST277），曾参与巴西的地方性暴发疫情。 结果 与既往报道的基因调控网络相比，本研究获得的网络包含更多的调控基因、靶基因与相互作用关系。拓扑分析结果符合生物过程的复杂网络表征特征。 主要结论 该网络的属性与铜绿假单胞菌的生物学特征相符。据我们所知，本研究构建的铜绿假单胞菌基因调控网络是目前已公开的最完整版本。