Fructose-1,6-Bisphosphate Reduces the Mortality in Candida albicans Bloodstream Infection and Prevents the Septic-Induced Platelet Decrease

Santos, Roberto Christ Vianna; Moresco, Rafael Noal; Rico, Miguel Ángel; Susperregui, Antonio R.G.; Rosa, José Luís; Bartrons, Ramón; Ventura, Francesc; Mário, Débora Nunes; Alves, Sydney Hartz; Tatsch, Etiane; Kober, Helena; Mello, Ricardo Obalski de; Scherer, Patricia; Dias, Henrique Bregolin; Oliveira, Jarbas Rodrigues de

doi:10.1007/s10753-012-9436-7

Cited by 10 publications

(5 citation statements)

References 27 publications

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“…Additionally, fructose-1,6-bisphosphate (F16BP) has been shown to prevent mortality from active Candida albicans bloodstream infection in mice. 60 Interestingly, the levels of F16BP were reduced by almost 60% in VF patients as compared with controls. A further investigation of these candidate markers and their role in Coccidioides virulence and survival in a host environment is warranted.…”

Section: ■ Discussionmentioning

confidence: 91%

“…The levels of both metabolites were decreased by nearly 90% in VF patients as compared with controls. Additionally, fructose-1,6-bisphosphate (F16BP) has been shown to prevent mortality from active Candida albicans bloodstream infection in mice . Interestingly, the levels of F16BP were reduced by almost 60% in VF patients as compared with controls.…”

Section: Discussionmentioning

confidence: 99%

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Coccidioidomycosis Detection Using Targeted Plasma and Urine Metabolic Profiling

et al. 2019

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Coccidioidomycosis, also known as Valley fever (VF), is a potentially lethal fungal infection that results in more than 200 deaths per year in the United States. Despite the important role of metabolic processes in the molecular pathogenesis of VF, robust metabolic markers to enable effective screening, rapid diagnosis, accurate surveillance, and therapeutic monitoring of VF are still lacking. We present a targeted liquid chromatography–tandem mass spectrometry-based metabolic profiling approach for identifying metabolic marker candidates that could enable rapid, highly sensitive, and specific VF detection. Using this targeted approach, 207 plasma metabolites and 231 urinary metabolites from many metabolic pathways of potential biological significance were reliably detected and monitored in 147 samples taken from two groups of subjects (48 VF patients and 99 non-VF controls). The results of our univariate significance testing and multivariate model development informed the construction of a three-metabolite panel of potential plasma biomarkers and a nine-metabolite panel of potential urinary biomarkers. Receiver operating characteristic curves generated based on orthogonal partial least-squares–discriminant analysis models showed excellent classification performance, with 94.4% sensitivity and 97.6% specificity for plasma metabolites. Urine metabolites were less accurate, demonstrating 89.7% sensitivity and 88.1% specificity. Enrichment, pathway, and network analyses revealed significant disturbances in glycine and serine metabolism, in both plasma and urine samples. To the best of our knowledge, this is the first study aiming to discover novel metabolite markers of VF, which could achieve accurate diagnosis within 24 h. The results expand the basic knowledge of the metabolome related to VF and potentially reveal pathways or markers that could be therapeutically targeted. This study also provides a promising basis for the development of larger multisite projects to validate our findings across population groups and further advance the development of better clinical care for VF patients.

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Section: ■ Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Coccidioidomycosis Detection Using Targeted Plasma and Urine Metabolic Profiling

et al. 2019

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“…Male mice (eight week old, C57Bl/6N, 25-30g) maintained in a 12h light-dark cycle with water and chow ad libitum , were divided into four groups; 1) Bleomycin (BLM) group: received intratracheally (IT) 1.2U/kg BLM (Sigma-Aldrich) on day 0 [17], 2) control group: received IT an equal volume of saline on day 0, 3) BLM + FBP group; BLM IT on day 0 and thereafter daily intraperitoneal injection (ip) of 500 mg/kg FBP [16, 18] for 14 days, and 4) FBP group: saline IT on day 0 and thereafter daily ip of FBP. Weight and mortality were monitored daily for 14 days.…”

Section: Methodsmentioning

confidence: 99%

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

et al. 2019

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Pulmonary fibrosis (PF) is the result of chronic injury where fibroblasts become activated and secrete large amounts of extracellular matrix (ECM), leading to impaired fibroblasts degradation followed by stiffness and loss of lung function. Fructose-1,6-bisphosphate (FBP), an intermediate of glycolytic pathway, decreases PF development, but the underlying mechanism is unknown. To address this issue, PF was induced in vivo using a mouse model, and pulmonary fibroblasts were isolated from healthy and fibrotic animals. In PF model mice, lung function was improved by FBP as revealed by reduced collagen deposition and downregulation of ECM gene expression such as collagens and fibronectin. Fibrotic lung fibroblasts (FLF) treated with FBP for 3 days in vitro showed decreased proliferation, contraction, and migration, which are characteristic of myofibroblast to fibroblast phenotype reversal. ECM-related genes and proteins such as collagens, fibronectin and α-smooth muscle actin, were also downregulated in FBP-treated FLF. Moreover, matrix metalloproteinase (MMP) 1, responsible for ECM degradation, was produced only in fibroblasts obtained from healthy lungs (HLF) and FBP did not alter its expression. On the other hand, tissue inhibitor of metalloproteinase (TIMP)-1, a MMP1 inhibitor, and MMP2, related to fibroblast tissue-invasion, were predominantly produced by FLF and FBP was able to downregulate its expression. These results demonstrate that FBP may prevent bleomycin-induced PF development through reduced expression of collagen and other ECM components mediated by a reduced TIMP-1 and MMP2 expression.

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“…Fructose-1,6-bisphosphate (FBP), a glycolytic metabolite, is reported to have salutary effects in a variety of pathologic situations such as sepsis [12,13] and ischemia/reperfusion injury [14][15][16]. It was proposed that FBP exerts its protective role through the preservation of ATP levels by serving as a high energy substrate under pathologic conditions [14,[17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Fructose-1,6-bisphosphate suppresses lipopolysaccharide-induced expression of ICAM-1 through modulation of toll-like receptor-4 signaling in brain endothelial cells

Seok

Park

et al. 2015

International Immunopharmacology

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Fructose-1,6-Bisphosphate Reduces the Mortality in Candida albicans Bloodstream Infection and Prevents the Septic-Induced Platelet Decrease

Cited by 10 publications

References 27 publications

Coccidioidomycosis Detection Using Targeted Plasma and Urine Metabolic Profiling

Coccidioidomycosis Detection Using Targeted Plasma and Urine Metabolic Profiling

Fructose-1,6-bisphosphate prevents pulmonary fibrosis by regulating extracellular matrix deposition and inducing phenotype reversal of lung myofibroblasts

Fructose-1,6-bisphosphate suppresses lipopolysaccharide-induced expression of ICAM-1 through modulation of toll-like receptor-4 signaling in brain endothelial cells

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