A curated collection of Klebsiella metabolic models reveals variable substrate usage and gene essentiality
- Jane Hawkey1,
- Ben Vezina1,
- Jonathan M. Monk2,
- Louise M. Judd1,
- Taylor Harshegyi1,
- Sebastián López-Fernández3,
- Carla Rodrigues3,
- Sylvain Brisse3,
- Kathryn E. Holt1,4 and
- Kelly L. Wyres1
- 1Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia;
- 2Department of Bioengineering, University of California, San Diego, San Diego, California 92093, USA;
- 3Institut Pasteur, Université de Paris, Biodiversity and Epidemiology of Bacterial Pathogens, 75015 Paris, France;
- 4Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
Abstract
The Klebsiella pneumoniae species complex (KpSC) is a set of seven Klebsiella taxa that are found in a variety of niches and are an important cause of opportunistic health care–associated infections in humans. Because of increasing rates of multi-drug resistance within the KpSC, there is a growing interest in better understanding the biology and metabolism of these organisms to inform novel control strategies. We collated 37 sequenced KpSC isolates isolated from a variety of niches, representing all seven taxa. We generated strain-specific genome-scale metabolic models (GEMs) for all 37 isolates and simulated growth phenotypes on 511 distinct carbon, nitrogen, sulfur, and phosphorus substrates. Models were curated and their accuracy was assessed using matched phenotypic growth data for 94 substrates (median accuracy of 96%). We explored species-specific growth capabilities and examined the impact of all possible single gene deletions using growth simulations in 145 core carbon substrates. These analyses revealed multiple strain-specific differences, within and between species, and highlight the importance of selecting a diverse range of strains when exploring KpSC metabolism. This diverse set of highly accurate GEMs could be used to inform novel drug design, enhance genomic analyses, and identify novel virulence and resistance determinants. We envisage that these 37 curated strain-specific GEMs, covering all seven taxa of the KpSC, provide a valuable resource to the Klebsiella research community.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.276289.121.
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Freely available online through the Genome Research Open Access option.
- Received October 13, 2021.
- Accepted March 8, 2022.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
