Exposure to Sub-inhibitory Concentrations of the Chemosensitizer 1-(1-Naphthylmethyl)-Piperazine Creates Membrane Destabilization in Multi-Drug Resistant Klebsiella pneumoniae

Frontiers in Microbiology
João AnesShabarinath Srikumar

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 destabilized 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...Continue Reading

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Citations

Apr 15, 2021·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Ujjwal Jit KaurPraveen Rishi

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Datasets Mentioned

BETA
GSE122651
MGH78578

Methods Mentioned

BETA
RNA-seq
FCS
RNAseq
PCR
flow cytometry
transmission electron microscopy

Software Mentioned

FCS Express
HiSeq Control
CASAVA
DuctApe
De
GraphPad
R
limma
RTA
Integrated Genome Browser

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