Abstract The worldwide spread of bacterial infection and the emergence of resistance to antibiotics have become two major problems in the field of medical sciences. As a serious threat, antibiotic resistance genes, in addition to pathogenic bacteria, have been found in bacteria that are generally recognized as safe. One of the common mechanisms of multidrug resistance (MDR) is due to overexpression of efflux pumps. ATP- binding cassette (ABC) transporters are one type of efflux pumps which have an important role in bacterial MDR. ABC transporters mediate the antibiotic expel from the bacterial cell by hydrolyzing ATP. In order to study antibiotic resistance caused by ABC transporters and to capture molecular/gene networks activated/inactivated by any antibiotic, a RNA-seq analysis is performed on Escherichia coli ST131 which is treated by ciprofloxacin. Based on gene expression analysis, 589 genes expressed differentially (FDR p-value < 0.05). Totally 22 significant networks were extracted from differentially expressed genes (PPI < 0.05) which 3 of them have ABC transporters as enriched function including malEFG, lolCDE, and glnHPQ and the genes malG, lolE, and glnP are their hubs respectively. Among them, malEFG has two distinct enriched functions, ABC transporters and two-component system coincidently which means it is more likely to actively cooperate in antibiotic resistance. Since malEFG is up and two other networks are down regulated, ciprofloxacin can play the role of an activator for the first network and an inactivator for the others

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