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• W2912677344 abstract "Antimicrobial efflux is one of the important mechanisms causing multi-drug resistance (MDR) in bacteria. Chemosensitizers like 1-(1-naphthylmethyl)-piperazine (NMP) can inhibit an efflux pump and therefore can overcome MDR. However, secondary effects of NMP other than efflux pump inhibition are rarely investigated. Here, using phenotypic assays, phenotypic microarray and transcriptomic assays we show that NMP creates membrane destabilization in MDR Klebsiella pneumoniae MGH 78578 strain. The NMP mediated membrane destabilization activity was measured using β-Lactamase activity, membrane potential alteration studies and Transmission Electron Microscopy assays. Results from both β-Lactamase and membrane potential alteration studies shows that both outer and inner membranes are destabilised in NMP exposed K. pneumoniae MGH 78578 cells. Phenotypic Microarray and RNA-seq were further used to elucidate the metabolic and transcriptional signals underpinning membrane destabilization. Membrane destabilization happens as early as 15 min post-NMP treatment. Our RNA-seq data shows that many genes involved in envelope stress response were differentially regulated in the NMP treated cells. Up-regulation of genes encoding the envelope stress response and repair systems show the distortion in membrane homeostasis during survival in an environment containing sub-inhibitory concentration of NMP. In addition, the lsr operon encoding the production of autoinducer-2 responsible for biofilm production was down-regulated resulting in reduced biofilm formation in NMP treated cells, a phenotype confirmed by crystal violet-based assays. We postulate that the early membrane disruption leads to destabilization of inner membrane potential, impairing ATP production and consequently resulting in efflux pump inhibition." @default.
• W2912677344 created "2019-02-21" @default.
• W2912677344 creator A5002509043 @default.
• W2912677344 creator A5011573807 @default.
• W2912677344 creator A5017393792 @default.
• W2912677344 creator A5028954136 @default.
• W2912677344 creator A5058817939 @default.
• W2912677344 date "2019-02-13" @default.
• W2912677344 modified "2023-09-29" @default.
• W2912677344 title "Exposure to Sub-inhibitory Concentrations of the Chemosensitizer 1-(1-Naphthylmethyl)-Piperazine Creates Membrane Destabilization in Multi-Drug Resistant Klebsiella pneumoniae" @default.
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• W2912677344 doi "https://doi.org/10.3389/fmicb.2019.00092" @default.

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