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Background: The emergence of multidrug-resistant Klebsiella pneumoniae is a major public health concern. Many K. pneumoniae infections can only be treated when resorting to last-line drugs such as polymyxin B (PB). However, resistance to this antibiotic is also observed, although insufficient information is described on its mode of action as well as the mechanisms used by resistant bacteria to evade its effects. We aimed to study PB resistance and the influence of abiotic stresses in a clinical K. pneumoniae strain using whole transcriptome profiling. Results: We sequenced 12 cDNA libraries of K. pneumoniae Kp13 bacteria, from two biological replicates of the original strain Kp13 (Kp13) and five derivative strains: induced high-level PB resistance in acidic pH (Kp13pH), magnesium deprivation (Kp13Mg), high concentrations of calcium (Kp13Ca) and iron (Kp13Fe), and a control condition with PB (Kp13PolB). Our results show the involvement of multiple regulatory loci that differentially respond to each condition as well as a shared gene expression response elicited by PB treatment, and indicate the participation of two-regulatory components such as ArcA-ArcB, which could be involved in re-routing the K. pneumoniae metabolism following PB treatment. Modules of co-expressed genes could be determined, which correlated to growth in acid stress and PB exposure. We hypothesize that polymyxin B induces metabolic shifts in K. pneumoniae that could relate to surviving against the action of this antibiotic. Conclusions: We obtained whole transcriptome data for K. pneumoniae under different environmental conditions and PB treatment. Our results supports the notion that the K. pneumoniae response to PB exposure goes beyond damaged membrane reconstruction and involves recruitment of multiple gene modules and intracellular targets. [ABSTRACT FROM AUTHOR]

Drug repurposing has been applied in the biomedical field to optimize the use of existing drugs, leading to a more efficient allocation of research resources. In oncology, this approach is particularly interesting, considering the high cost related to the discovery of new drugs with therapeutic potential. Computational methods have been applied to predict associations between drugs and their targets. However, drug repurposing has not always been promising and its efficiency has yet to be proven. Therefore, the present scoping review protocol was developed to screen the literature on how in silico strategies can be implemented in drug repurposing in oncology. The scoping review will be conducted according to the Arksey and O'Malley framework (2005) and the Joanna Briggs Institute recommendations. We will search the PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We will include peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between January 1, 2003, and December 31, 2021. Data will be charted and findings described according to review questions. We will report the scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines (PRISMA-ScR). [ABSTRACT FROM AUTHOR]