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

Low, Ye Mun and Chong, Chun Wie and Yap, Ivan Kok Seng and Chai, Lay Ching and Clarke, Stuart C. and Ponnampalavanar, Sasheela and Jabar, Kartini Abdul and 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, 112 (7). pp. 378-386. ISSN 2047-7724, DOI https://doi.org/10.1080/20477724.2018.1538281.

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Official URL: https://doi.org/10.1080/20477724.2018.1538281


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 bla NDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1 H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1 H 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.

Item Type: Article
Funders: Fundamental Research Grant Scheme (FRGS) from the Ministry of Education, Malaysia (Grant number: FP023-2014A), University of Malaya Research Grant (UMRG) from University of Malaya (Grant number: RP026B-14HTM)
Uncontrolled Keywords: Carbapenem resistant Klebsiella pneumoniae; antibiotic resistance; phenotype microarrays; RNA-Seq; 1H NMR
Subjects: Q Science > QH Natural history
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 29 May 2019 03:42
Last Modified: 29 May 2019 03:42
URI: http://eprints.um.edu.my/id/eprint/21384

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