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PROVIDER: PRJNA508760 | ENA |
REPOSITORIES: ENA
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Project description:Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.
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Project description:Liao2011 - Genome-scale metabolic
reconstruction of Klebsiella pneumoniae (iYL1228)
This model is described in the article:
An experimentally validated
genome-scale metabolic reconstruction of Klebsiella pneumoniae
MGH 78578, iYL1228.
Liao YC, Huang TW, Chen FC,
Charusanti P, Hong JS, Chang HY, Tsai SF, Palsson BO, Hsiung
CA.
J. Bacteriol. 2011 Apr; 193(7):
1710-1717
Abstract:
Klebsiella pneumoniae is a Gram-negative bacterium of the
family Enterobacteriaceae that possesses diverse metabolic
capabilities: many strains are leading causes of
hospital-acquired infections that are often refractory to
multiple antibiotics, yet other strains are metabolically
engineered and used for production of commercially valuable
chemicals. To study its metabolism, we constructed a
genome-scale metabolic model (iYL1228) for strain MGH 78578,
experimentally determined its biomass composition,
experimentally determined its ability to grow on a broad range
of carbon, nitrogen, phosphorus and sulfur sources, and
assessed the ability of the model to accurately simulate growth
versus no growth on these substrates. The model contains 1,228
genes encoding 1,188 enzymes that catalyze 1,970 reactions and
accurately simulates growth on 84% of the substrates tested.
Furthermore, quantitative comparison of growth rates between
the model and experimental data for nine of the substrates also
showed good agreement. The genome-scale metabolic
reconstruction for K. pneumoniae presented here thus provides
an experimentally validated in silico platform for further
studies of this important industrial and biomedical
organism.
This model is hosted on
BioModels Database
and identified by:
MODEL1507180054.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-07-30 | MODEL1507180054 | BioModels
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to Klebsiella pneumoniae complex strains AJ055, AJ218, AJ292, KPC2, 03-311-0071 and 04153260899A.
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