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Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations

Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations
Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations

The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.

H NMR, antibiotic resistance, Carbapenem resistant Klebsiella pneumoniae, phenotype microarrays, RNA-Seq
2047-7724
1-9
Low, Ye Mun
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Chong, Chun Wie
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Yap, Ivan Kok Seng
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Chai, Lay Ching
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Clarke, Stuart C.
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Ponnampalavanar, Sasheela
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Abdul Jabar, Kartini
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Md Yusof, Mohd Yasim
f3566dc0-9be6-4c22-bad4-99d5b89d2512
Teh, Cindy Shuan Ju
33dcfb04-caa8-4103-a98a-476c831cca3c
Low, Ye Mun
8ad25102-db60-4ea5-8c26-571d32cbd0e3
Chong, Chun Wie
ac8fe83b-07c2-4c96-8fe4-65056115effe
Yap, Ivan Kok Seng
4ee6e2a7-0318-428c-a0bc-b4b05ed15a66
Chai, Lay Ching
2c978bbd-73ea-4a0b-92ec-a5e7e31c4a95
Clarke, Stuart C.
f7d7f7a2-4b1f-4b36-883a-0f967e73fb17
Ponnampalavanar, Sasheela
f43b5987-d07e-4c1d-9755-524886269b5f
Abdul Jabar, Kartini
ef310174-dfd1-4b1e-a87b-cf402e4374e2
Md Yusof, Mohd Yasim
f3566dc0-9be6-4c22-bad4-99d5b89d2512
Teh, Cindy Shuan Ju
33dcfb04-caa8-4103-a98a-476c831cca3c

Low, Ye Mun, Chong, Chun Wie, Yap, Ivan Kok Seng, Chai, Lay Ching, Clarke, Stuart C., Ponnampalavanar, Sasheela, Abdul Jabar, Kartini, Md Yusof, Mohd Yasim and Teh, Cindy Shuan Ju (2018) Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations. Pathogens and Global Health, 1-9. (doi:10.1080/20477724.2018.1538281).

Record type: Article

Abstract

The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.

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Elucidating the survival and response of carbapenem resistant Klebsiella pneumoniae after exposure to imipenem at sub-lethal concentrations
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Accepted/In Press date: 16 October 2018
e-pub ahead of print date: 31 October 2018
Keywords: H NMR, antibiotic resistance, Carbapenem resistant Klebsiella pneumoniae, phenotype microarrays, RNA-Seq

Identifiers

Local EPrints ID: 426245
URI: http://eprints.soton.ac.uk/id/eprint/426245
ISSN: 2047-7724
PURE UUID: 63c67ca9-bc1b-4864-bb38-46895749daab
ORCID for Stuart C. Clarke: ORCID iD orcid.org/0000-0002-7009-1548

Catalogue record

Date deposited: 20 Nov 2018 17:30
Last modified: 26 Nov 2021 06:58

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Contributors

Author: Ye Mun Low
Author: Chun Wie Chong
Author: Ivan Kok Seng Yap
Author: Lay Ching Chai
Author: Sasheela Ponnampalavanar
Author: Kartini Abdul Jabar
Author: Mohd Yasim Md Yusof
Author: Cindy Shuan Ju Teh

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