The novel potential multidrug-resistance biomarkers for Pseudomonas aeruginosa lung infections using transcriptomics data analysis

Abstract

Abstract Development of multidrug resistance is the main obstacle for treating infections of Pseudomonas aeruginosa, an opportunistic pathogen responsible for a wide range of persistent infections throughout the body. Hence, identifying the major genes contributing to the development of multidrug resistance in Pseudomonas aeruginosa could help to introduce new efficient drugs to prevent resistance development. Here we conducted a differential gene expression analysis and a series of systems biology investigations on a RNASeq data set of multidrug resistant Pseudomonas aeruginosa isolates obtained from the patients’ airways and wild-type, drug-sensitive strains. Respectively 67 and 178 up- and down-regulated genes were detected, including several genes of unknown functions that their functional characterization will help to elucidate the hidden mechanisms for multidrug resistance development in Pseudomonas aeruginosa. By inspecting the constructed gene regulatory network, two cases of feed forward loops were identified which in the case of establishing the type of regulatory interactions between transcription factors and their target genes, as activatory or inhibitory, their true contribution to multidrug resistance will be better understood. Inspecting the constructed gene co-expression network revealed co-expression between four deregulated genes including PA14_32830, PA14_03380, fpvA and PA14_15610 and four already known drug resistance biomarkers. Functional characterization of these four co-expressed genes, will elucidate their possible roles in the process of multidrug resistance development in Pseudomonas aeruginosa. These findings will suggest new potential multidrug resistance biomarkers that following confirmation by larger number of samples, can be considered as new promising drug targets.