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Systems Biology of Metabolism in Infections

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Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00161

Comparative Genome-scale Metabolic Modelling of Metallo-beta-Lactamase–producing Multidrug-resistant Klebsiella pneumoniae Clinical Isolates

 Charles J. Norsigian1, 2,  Heba Attia3, 4, Richard Szubin2, Aymin Yassin3, 4,  Bernhard O. Palsson2,  Ramy K. Aziz3, 4 and  Jonathan Monk2*
  • 1University of California, San Diego, United States
  • 2Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, United States
  • 3Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Egypt
  • 4The Center for Microbiome and Genome Research, Cairo University, Egypt

The emergence and spread of metallo-beta-lactamase–producing multidrug-resistant Klebsiella pneumoniae is a serious public health threat, which is further complicated by the increased prevalence of colistin resistance. The link between antimicrobial resistance acquired by strains of Klebsiella and their unique metabolic capabilities has not been determined. Here, we reconstruct genome-scale metabolic models for 22 K. pneumoniae strains with various resistances to different antibiotics including two strains exhibiting colistin resistance isolated from Cairo, Egypt. We use the models to predict growth capabilities on 265 different sole carbon, nitrogen, sulfur, and phosphorus sources for all 22 strains. Alternate nitrogen source utilization of glutamate, arginine, histidine and ethanolamine among others provided discriminatory power for predicting resistance to amikacin, tetracycline and gentamicin. Thus, genome-scale model based predictions of growth capabilities on alternative substrates may lead to construction of robust classification trees that are predictive of antibiotic resistance in Klebsiella isolates.

Keywords: multi-drug resistance, Klebsiella pneumoniae, Genome-scale modelling, Colistin, MDR

Received: 16 Jan 2019; Accepted: 29 Apr 2019.

Edited by:

Gianni Panagiotou, Leibniz Institute for Natural Product Research and Infection Biology, Germany

Reviewed by:

Thomas Dandekar, University of Wuerzburg, Germany
Christoph Kaleta, University of Kiel, Germany  

Copyright: © 2019 Norsigian, Attia, Szubin, Yassin, Palsson, Aziz and Monk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jonathan Monk, Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, 92093, California, United States,