Abstract
BackgroundThe 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.ResultsWe 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3070-y) contains supplementary material, which is available to authorized users.
Highlights
The emergence of multidrug-resistant Klebsiella pneumoniae is a major public health concern
While genome analyses provide a complete picture of the genes present, only through the use of high throughput expression profiling techniques such as RNA sequencing (RNA-seq), as performed in this report, can we find consistent expression patterns that can aid in pinpointing the intracellular targets and metabolic processes related to polymyxin B mode of action and resistance
We were interested in detecting additional mechanisms of resistance to this antibiotic as well as understand the effect of polymyxin B (PB) treatment combined with diverse abiotic stresses in the global gene expression response of K. pneumoniae
Summary
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). Resistance to this antibiotic is observed, insufficient information is described on its mode of action as well as the mechanisms used by resistant bacteria to evade its effects. There were ever increasing numbers of bacteria that could overcome treatment and displayed a resistant phenotype. Extreme cases involve bacteria that display resistance against all clinically available agents [2]. The emergence of resistance pre-dates the antibiotic era, widespread multi-drug resistance (MDR) is a major concern that limit therapeutic options in the treatment of many bacterial infections. It has been reported that PB activity may involve inhibition of vital respiratory enzymes located in the inner membrane, such as NADH-quinone oxidoreductase (NDH-2) [5], thereby hampering bacterial respiration
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