Abstract
BackgroundYersinia pestis is a gram-negative bacterium that causes plague, a disease linked historically to the Black Death in Europe during the Middle Ages and to several outbreaks during the modern era. Metabolism in Y. pestis displays remarkable flexibility and robustness, allowing the bacterium to proliferate in both warm-blooded mammalian hosts and cold-blooded insect vectors such as fleas.ResultsHere we report a genome-scale reconstruction and mathematical model of metabolism for Y. pestis CO92 and supporting experimental growth and metabolite measurements. The model contains 815 genes, 678 proteins, 963 unique metabolites and 1678 reactions, accurately simulates growth on a range of carbon sources both qualitatively and quantitatively, and identifies gaps in several key biosynthetic pathways and suggests how those gaps might be filled. Furthermore, our model presents hypotheses to explain certain known nutritional requirements characteristic of this strain.ConclusionsY. pestis continues to be a dangerous threat to human health during modern times. The Y. pestis genome-scale metabolic reconstruction presented here, which has been benchmarked against experimental data and correctly reproduces known phenotypes, provides an in silico platform with which to investigate the metabolism of this important human pathogen.
Highlights
Yersinia pestis is a gram-negative bacterium that causes plague, a disease linked historically to the Black Death in Europe during the Middle Ages and to several outbreaks during the modern era
Characteristics of the reconstruction The Y. pestis CO92 metabolic reconstruction presented here, iPC815, contains 815 genes, 678 proteins, 963 unique metabolites, and 1678 reactions. iPC815 was assembled by comparison to existing E. coli [8], Salmonella enterica serovar Typhimurium
Typhimurium) [9], and Y. pestis strain 91001 [7] metabolic reconstructions; genetic, protein, metabolite, and biochemical data contained in databases such as KEGG [10], BRENDA [11], MetaCyc [12], and PATRIC [13]; and genus, species, and strain-specific information gleaned from the literature
Summary
Yersinia pestis is a gram-negative bacterium that causes plague, a disease linked historically to the Black Death in Europe during the Middle Ages and to several outbreaks during the modern era. Yersinia pestis is a gram-negative bacterium within the family Enterobacteriaceae that, along with Yersinia pseudotuberculosis and Yersinia enterocolitica, is one of three members of its genus that can cause disease in humans. Y. pestis diverged from Y. pseudotuberculosis only 1,500 - 20,000 years ago, but Y. pestis and Y. pseudotuberculosis diverged from Y. enterocolitica in the more distant past [1] Despite their close evolutionary relationship, the diseases they cause differ markedly. Biovar Antigua is associated with the Justinian plague; biovar Mediavalis is associated with the Black Death; and biovar Orientalis is associated with modern plague [5]. Debate surrounding these associations continues, as recent data suggest that the Black Death might not have been caused by strains belonging to Biovar Mediavalis but rather by at least two strains that pre-date the emergence of and are distinct from both biovar Mediavalis and biovar Orientalis [6]
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