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http://dx.doi.org/10.3839/jabc.2015.035

L-glutamine:D-fructose-6-phosphate Aminotransferase as a Key Protein Linked to Multidrug Resistance in E. coli KD43162  

Lee, Sung-Eun (School of Applied Biosciences, Kyungpook National University)
Jung, Tae-Jeon (Department of Laboratory Medicine, Kosin University Gospel Hospital College of Medicine)
Park, Byeoung-Soo (Research Station, Nanotoxtech Inc.)
Kim, Byung-Woo (Department of Life Science and Biotechnology, Dongeui University)
Lee, Eun-Woo (Department of Life Science and Biotechnology, Dongeui University)
Kim, Hye Jin (Department of Dental Hygiene, Dongeui University)
Yum, Jong Hwa (Department of Clinical Laboratory Science, Dongeui University)
Publication Information
Journal of Applied Biological Chemistry / v.58, no.3, 2015 , pp. 227-232 More about this Journal
Abstract
A microarray study has been employed to understand changes of gene expression in E. coli KD43162 resistant to ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, cefazolin, cefepime, aztreonam, imipenem, meropenem, gentamicin, tobramycin, ciprofloxacin, levofloxacin, moxifloxacin, fosfomycin, and trimethoprim-sulfamethoxazole except for amikacin using disk diffusion assay. Using Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and MALDI-TOF MS analyses, 36 kDa of outer membrane proteins (OMPs) was found to be deleted in the multidrug resistant E. coli KD 43162. Microarray analysis was used to determine up- and down-regulated genes in relation to multidrug resistant E. coli KD43162. Among the up-regulated genes, these genes were corresponded to express the proteins as penicillin-binding proteins (PBPs), tartronate semialdehyde reductase, ethanolamine utilization protein, shikimate kinase I, allantoinase, predicted SAM-dependent methyltransferase, L-glutamine: D-fructose-6-phosphate aminotransferase (GFAT), phospho-glucosamine mutase, predicted N-acetylmannosamine kinase, and predicted N-acetylmannosamine-6-P epimerase. Up-regulation of PBPs, one of primary target sites of antibiotics, might be responsible for the multidrug resistance in E. coli with increasing amount of target sites. Up-regulation of GFAT enzyme may be related to the up-regulation of PBPs because GFAT produces N-acetylglucosamine, a precursor of peptidoglycans. One of GFAT inhibitors, azaserine, showed a potent inhibition on the growth of E. coli KD43162. In conclusion, up-regulation of PBPs and GFATs with the loss of 36 kDa OMP refers the multidrug resistance in E. coli KD 43162.
Keywords
E. coli; genomics; L-glutamine:D-fructose-6-phosphate aminotransferase; multidrug resistance;
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