Dataset Information

Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

ABSTRACT: Bacteremia, the presence of viable bacteria in the blood stream, is often associated with several clinical conditions. Bacteremia can lead to multiple organ failure if managed incorrectly, which makes providing suitable nutritional support vital for reducing bacteremia-associated mortality. In order to provide such information, we investigated the metabolic consequences of a Klebsiella pneumoniae (K. pneumoniae) infection in vivo by employing a combination of (1)H nuclear magnetic resonance spectroscopy and multivariate data analysis. K. pneumoniae was intravenously infused in rats; urine and plasma samples were collected at different time intervals. We found that K. pneumoniae-induced bacteremia stimulated glycolysis and the tricarboxylic acid cycle and also promoted oxidation of fatty acids and creatine phosphate to facilitate the energy-demanding host response. In addition, K. pneumoniae bacteremia also induced anti-endotoxin, anti-inflammatory and anti-oxidization responses in the host. Furthermore, bacteremia could cause a disturbance in the gut microbiotal functions as suggested by alterations in a range of amines and bacteria-host co-metabolites. Our results suggest that supplementation with glucose and a high-fat and choline-rich diet could ameliorate the burdens associated with bacteremia. Our research provides underlying pathological processes of bacteremia and a better understanding of the clinical and biochemical manifestations of bacteremia.

SUBMITTER: Dong F

PROVIDER: S-EPMC3511377 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

Dong Fangcong F Wang Bin B Zhang Lulu L Tang Huiru H Li Jieshou J Wang Yulan Y

PloS one 20121130 11

Bacteremia, the presence of viable bacteria in the blood stream, is often associated with several clinical conditions. Bacteremia can lead to multiple organ failure if managed incorrectly, which makes providing suitable nutritional support vital for reducing bacteremia-associated mortality. In order to provide such information, we investigated the metabolic consequences of a Klebsiella pneumoniae (K. pneumoniae) infection in vivo by employing a combination of (1)H nuclear magnetic resonance spec ...[more]

PMID: 23226457

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Project description:The Klebsiella pneumoniae species complex (KpSC) is a major source of nosocomial infections globally with high rates of resistance to antimicrobials. Consequently, there is growing interest in understanding virulence factors and their association with cellular metabolic processes for developing novel anti-KpSC therapeutics. Phenotypic assays have revealed metabolic diversity within the KpSC, but metabolism research has been neglected due to experiments being difficult and cost-intensive. Genome-scale metabolic models (GSMMs) represent a rapid and scalable in silico approach for exploring metabolic diversity, which compile genomic and biochemical data to reconstruct the metabolic network of an organism. Here we use a diverse collection of 507 KpSC isolates, including representatives of globally distributed clinically relevant lineages, to construct the most comprehensive KpSC pan-metabolic model to date, KpSC pan v2. Candidate metabolic reactions were identified using gene orthology to known metabolic genes, prior to manual curation via extensive literature and database searches. The final model comprised a total of 3550 reactions, 2403 genes and can simulate growth on 360 unique substrates. We used KpSC pan v2 as a reference to derive strain-specific GSMMs for all 507 KpSC isolates, and compared these to GSMMs generated using a prior KpSC pan-reference (KpSC pan v1) and two single-strain references. We show that KpSC pan v2 includes a greater proportion of accessory reactions (8.8 %) than KpSC pan v1 (2.5 %). GSMMs derived from KpSC pan v2 also generate more accurate growth predictions, with high median accuracies of 95.4 % (aerobic, n=37 isolates) and 78.8 % (anaerobic, n=36 isolates) for 124 matched carbon substrates. KpSC pan v2 is freely available at https://github.com/kelwyres/KpSC-pan-metabolic-model, representing a valuable resource for the scientific community, both as a source of curated metabolic information and as a reference to derive accurate strain-specific GSMMs. The latter can be used to investigate the relationship between KpSC metabolism and traits of interest, such as reservoirs, epidemiology, drug resistance or virulence, and ultimately to inform novel KpSC control strategies.

Project description:Klebsiella pneumoniae has become an important pathogen in recent years. Although most cases of K. pneumoniae endogenous endophthalmitis occur via hematogenous spread, it is not yet clear which microbial and host factors are responsible for the ability of K. pneumoniae to cross the blood-retinal barrier (BRB). In the present study, we show that in an in vitro model of BRB based on coculturing primary bovine retinal endothelial cells (BREC) and primary bovine retinal pericytes (BRPC), K. pneumoniae infection determines changes of transendothelial electrical resistance (TEER) and permeability to sodium fluorescein. In the coculture model, bacteria are able to stimulate the enzyme activities of endothelial cytosolic and Ca(2+)-independent phospholipase A2s (cPLA2 and iPLA2). These results were confirmed by the incremental expression of cPLA2, iPLA2, cyclo-oxygenase-1 (COX1), and COX2 in BREC, as well as by cPLA2 phosphorylation. In supernatants of K. pneumoniae-stimulated cocultures, increases in prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-8, and vascular endothelial growth factor (VEGF) production were found. Incubation with K. pneumoniae in the presence of arachidonoyl trifluoromethyl ketone (AACOCF3) or bromoenol lactone (BEL) caused decreased PGE2 and VEGF release. Scanning electron microscopy and transmission electron microscopy images of BREC and BRPC showed adhesion of K. pneumoniae to the cells, but no invasion occurred. K. pneumoniae infection also produced reductions in pericyte numbers; transfection of BREC cocultured with BRPC and of human retinal endothelial cells (HREC) cocultured with human retinal pericytes (HRPC) with small interfering RNAs (siRNAs) targeted to cPLA2 and iPLA2 restored the pericyte numbers and the TEER and permeability values. Our results show the proinflammatory effect of K. pneumoniae on BREC, suggest a possible mechanism by which BREC and BRPC react to the K. pneumoniae infection, and may provide physicians and patients with new ways of fighting blinding diseases.

Dataset Information

Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

Publications

Metabolic response to Klebsiella pneumoniae infection in an experimental rat model.

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