Central carbon metabolism of Leishmania parasites

Parasitology ◽  
2010 ◽  
Vol 137 (9) ◽  
pp. 1303-1313 ◽  
Author(s):  
ELEANOR C. SAUNDERS ◽  
DAVID P. DE SOUZA ◽  
THOMAS NADERER ◽  
MARIJKE F. SERNEE ◽  
JULIE E. RALTON ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Drug Targets ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
Mammalian Host ◽  
Insect Vector ◽  
Carbon Utilization ◽  
Central Carbon ◽  
Host Infection

SUMMARYLeishmania spp. are sandfly-transmitted protozoa parasites that cause a spectrum of diseases in humans. Many enzymes involved in Leishmania central carbon metabolism differ from their equivalents in the mammalian host and are potential drug targets. In this review we summarize recent advances in our understanding of Leishmania central carbon metabolism, focusing on pathways of carbon utilization that are required for growth and pathogenesis in the mammalian host. While Leishmania central carbon metabolism shares many features in common with other pathogenic trypanosomatids, significant differences are also apparent. Leishmania parasites are also unusual in constitutively expressing most core metabolic pathways throughout their life cycle, a feature that may allow these parasites to exploit a range of different carbon sources (primarily sugars and amino acids) rapidly in both the insect vector and vertebrate host. Indeed, recent gene deletion studies suggest that mammal-infective stages are dependent on multiple carbon sources in vivo. The application of metabolomic approaches, outlined here, are likely to be important in defining aspects of central carbon metabolism that are essential at different stages of mammalian host infection.

scholarly journals Comparative metabolomics of Phialemonium curvatum as an omnipotent fungus cultivated on crude palm oil versus glucose

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Arief Izzairy Zamani ◽  
Susann Barig ◽  
Sarah Ibrahim ◽  
Hirzun Mohd. Yusof ◽  
Julia Ibrahim ◽  
...  
Keyword(s):  
Carbon Source ◽  
Organic Acids ◽  
Vegetable Oil ◽  
Carbon Metabolism ◽  
Sole Carbon Source ◽  
Carbon Sources ◽  
Tca Cycle ◽  
Central Carbon Metabolism ◽  
Targeted Metabolomics ◽  
Central Carbon

Abstract Background Sugars and triglycerides are common carbon sources for microorganisms. Nonetheless, a systematic comparative interpretation of metabolic changes upon vegetable oil or glucose as sole carbon source is still lacking. Selected fungi that can grow in acidic mineral salt media (MSM) with vegetable oil had been identified recently. Hence, this study aimed to investigate the overall metabolite changes of an omnipotent fungus and to reveal changes at central carbon metabolism corresponding to both carbon sources. Results Targeted and non-targeted metabolomics for both polar and semi-polar metabolites of Phialemonium curvatum AWO2 (DSM 23903) cultivated in MSM with palm oil (MSM-P) or glucose (MSM-G) as carbon sources were obtained. Targeted metabolomics on central carbon metabolism of tricarboxylic acid (TCA) cycle and glyoxylate cycle were analysed using LC–MS/MS-TripleQ and GC–MS, while untargeted metabolite profiling was performed using LC–MS/MS-QTOF followed by multivariate analysis. Targeted metabolomics analysis showed that glyoxylate pathway and TCA cycle were recruited at central carbon metabolism for triglyceride and glucose catabolism, respectively. Significant differences in organic acids concentration of about 4- to 8-fold were observed for citric acid, succinic acid, malic acid, and oxaloacetic acid. Correlation of organic acids concentration and key enzymes involved in the central carbon metabolism was further determined by enzymatic assays. On the other hand, the untargeted profiling revealed seven metabolites undergoing significant changes between MSM-P and MSM-G cultures. Conclusions Overall, this study has provided insights on the understanding on the effect of triglycerides and sugar as carbon source in fungi global metabolic pathway, which might become important for future optimization of carbon flux engineering in fungi to improve organic acids production when vegetable oil is applied as the sole carbon source.

scholarly journals The Functional Structure of Central Carbon Metabolism in Pseudomonas putida KT2440

2014 ◽  
Vol 80 (17) ◽  
pp. 5292-5303 ◽  
Author(s):  
Suresh Sudarsan ◽  
Sarah Dethlefsen ◽  
Lars M. Blank ◽  
Martin Siemann-Herzberg ◽  
Andreas Schmid
Keyword(s):  
Pseudomonas Putida ◽  
Carbon Metabolism ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
Transcriptional Level ◽  
Regulation Mechanism ◽  
Central Metabolism ◽  
Content Type ◽  
Central Carbon ◽  
Definition Of

ABSTRACTWhat defines central carbon metabolism? The classic textbook scheme of central metabolism includes the Embden-Meyerhof-Parnas (EMP) pathway of glycolysis, the pentose phosphate pathway, and the citric acid cycle. The prevalence of this definition of central metabolism is, however, equivocal without experimental validation. We address this issue using a general experimental approach that combines the monitoring of transcriptional and metabolic flux changes between steady states on alternative carbon sources. This approach is investigated by using the model bacteriumPseudomonas putidawith glucose, fructose, and benzoate as carbon sources. The catabolic reactions involved in the initial uptake and metabolism of these substrates are expected to show a correlated change in gene expressions and metabolic fluxes. However, there was no correlation for the reactions linking the 12 biomass precursor molecules, indicating a regulation mechanism other than mRNA synthesis for central metabolism. This result substantiates evidence for a (re)definition of central carbon metabolism including all reactions that are bound to tight regulation and transcriptional invariance. Contrary to expectations, the canonical Entner-Doudoroff and EMP pathwayssensu strictoare not a part of central carbon metabolism inP. putida, as they are not regulated differently from the aromatic degradation pathway. The regulatory analyses presented here provide leads on a qualitative basis to address the use of alternative carbon sources by deregulation and overexpression at the transcriptional level, while rate improvements in central carbon metabolism require careful adjustment of metabolite concentrations, as regulation resides to a large extent in posttranslational and/or metabolic regulation.

scholarly journals A Functional cra Gene Is Required forSalmonella enterica Serovar Typhimurium Virulence in BALB/c Mice

2000 ◽  
Vol 68 (6) ◽  
pp. 3772-3775 ◽  
Author(s):  
James H. Allen ◽  
Maryjane Utley ◽  
Han van den Bosch ◽  
Piet Nuijten ◽  
Maarten Witvliet ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Salmonella Enterica ◽  
Protein A ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
Central Carbon ◽  
Serovar Typhimurium ◽  
Gluconeogenic Substrates

ABSTRACT A minitransposon mutant of Salmonella enterica serovar Typhimurium SR-11, SR-11 Fad−, is unable to utilize gluconeogenic substrates as carbon sources and is avirulent and immunogenic when administered perorally to BALB/c mice (M. J. Utley et al., FEMS Microbiol. Lett., 163:129–134, 1998). Here, evidence is presented that the mutation in SR-11 Fad− that renders the strain avirulent is in the cra gene, which encodes the Cra protein, a regulator of central carbon metabolism.

scholarly journals Investigation into the flux distribution of central carbon metabolism in Corynebacterium glutamicum using principal component analysis

2015 ◽  
Vol 67 (3) ◽  
pp. 767-774
Author(s):  
Chuanyu Shang ◽  
Xiangfei Zhou ◽  
Wenwei Zhou ◽  
Xiaoyao Xie ◽  
Yin Yi
Keyword(s):  
Corynebacterium Glutamicum ◽  
Carbon Metabolism ◽  
Flux Distribution ◽  
Environmental Changes ◽  
Principal Component ◽  
Central Carbon Metabolism ◽  
Preliminary Examination ◽  
Genetic Modifications ◽  
Central Carbon

Central carbon metabolism is the main source of energy required by organisms and it provides precursors for other in vivo metabolic processes. The flux flowing through the pathways involved in central carbon metabolism characterizes its biological function and genetic readout between species or environments. In recent years, using a 13C tracer technique, researchers have measured the flux of central carbon metabolism in Corynebacterium glutamicum under a variety of nutritional and environmental changes or genetic modifications. However, there is no integrated and comparative analysis of these measured flux values. In this study, the flux values of central carbon metabolism in Corynebacterium glutamicum that were obtained in other recent studies were consolidated. A preliminary examination of the distribution characteristics of flux values in each metabolic pathway was conducted and the regression relationship between different fluxes was investigated. The principal components of the flux vector were further extracted and aggregated based on the components, and the general features of flux distribution of central carbon metabolism as well as the influence of environmental and genetic factors on the flux distribution were determined. This study provides a foundation for further investigation into the flux distribution and regulation characteristics of central carbon metabolism.

scholarly journals Ex vivo and in vivo stable isotope labelling of central carbon metabolism and related pathways with analysis by LC–MS/MS

2019 ◽  
Vol 14 (2) ◽  
pp. 313-330 ◽  
Author(s):  
Min Yuan ◽  
Daniel M. Kremer ◽  
He Huang ◽  
Susanne B. Breitkopf ◽  
Issam Ben-Sahra ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Carbon Metabolism ◽  
Ex Vivo ◽  
Central Carbon Metabolism ◽  
Stable Isotope Labelling ◽  
Isotope Labelling ◽  
Central Carbon

scholarly journals Evidence for loss and adaptive reacquisition of alcoholic fermentation in an early-derived fructophilic yeast lineage

2017 ◽  
Author(s):  
Carla Gonçalves ◽  
Jennifer H. Wisecaver ◽  
Madalena Salema-Oom ◽  
Maria José Leandro ◽  
Xing-Xing Shen ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Carbon Metabolism ◽  
Alcoholic Fermentation ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
High Sugar ◽  
Central Carbon ◽  
Adaptive Nature

AbstractFructophily is a rare trait that consists in the preference for fructose over other carbon sources. Here we show that in a yeast lineage (theWickerhamiella/Starmerella, W/S clade) formed by fructophilic species thriving in the floral niche, the acquisition of fructophily is part of a wider process of adaptation of central carbon metabolism to the high sugar environment. Coupling comparative genomics with biochemical and genetic approaches, we show that the alcoholic fermentation pathway was profoundly remodeled in the W/S clade, as genes required for alcoholic fermentation were lost and subsequently re-acquired from bacteria through horizontal gene transfer. We further show that the reinstated fermentative pathway is functional and that an enzyme required for sucrose assimilation is also of bacterial origin, reinforcing the adaptive nature of the genetic novelties identified in the W/S clade. This work shows how even central carbon metabolism can be remodeled by a surge of HGT events.

scholarly journals Mutations in Alternative Carbon Utilization Pathways in Candida albicans Attenuate Virulence and Confer Pleiotropic Phenotypes

2006 ◽  
Vol 6 (2) ◽  
pp. 280-290 ◽  
Author(s):  
Melissa A. Ramírez ◽  
Michael C. Lorenz
Keyword(s):  
Candida Albicans ◽  
Carbon Metabolism ◽  
Innate Immune System ◽  
Glyoxylate Cycle ◽  
Transcriptional Profiling ◽  
Carbon Sources ◽  
Innate Immune ◽  
Carbon Utilization ◽  
The Glyoxylate Cycle

ABSTRACT The interaction between Candida albicans and cells of the innate immune system is a key determinant of disease progression. Transcriptional profiling has revealed that C. albicans has a complex response to phagocytosis, much of which is similar to carbon starvation. This suggests that nutrient limitation is a significant stress in vivo, and we have shown that glyoxylate cycle mutants are less virulent in mice. To examine whether other aspects of carbon metabolism are important in vivo during an infection, we have constructed strains lacking FOX2 and FBP1, which encode key components of fatty acid β-oxidation and gluconeogenesis, respectively. As expected, fox2Δ mutants failed to utilize several fatty acids as carbon sources. Surprisingly, however, these mutants also failed to grow in the presence of several other carbon sources, whose assimilation is independent of β-oxidation, including ethanol and citric acid. Mutants lacking the glyoxylate enzyme ICL1 also had more severe carbon utilization phenotypes than were expected. These results suggest that the regulation of alternative carbon metabolism in C. albicans is significantly different from that in other fungi. In vivo, fox2Δ mutants show a moderate but significant reduction in virulence in a mouse model of disseminated candidiasis, while disruption of the glyoxylate cycle or gluconeogenesis confers a severe attenuation in this model. These data indicate that C. albicans often encounters carbon-poor conditions during growth in the host and that the ability to efficiently utilize multiple nonfermentable carbon sources is a virulence determinant. Consistent with this in vivo requirement, C. albicans uniquely regulates carbon metabolism in a more integrated manner than in Saccharomyces cerevisiae, such that defects in one part of the machinery have wider impacts than expected. These aspects of alternative carbon metabolism may then be useful as targets for therapeutic intervention.

Lighting Up Live-Cell and In Vivo Central Carbon Metabolism with Genetically Encoded Fluorescent Sensors

2020 ◽  
Vol 13 (1) ◽  
pp. 293-314 ◽  
Author(s):  
Zhuo Zhang ◽  
Xiawei Cheng ◽  
Yuzheng Zhao ◽  
Yi Yang
Keyword(s):  
Carbon Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Central Carbon Metabolism ◽  
Fluorescent Sensors ◽  
Pentose Phosphate ◽  
Spatiotemporal Information ◽  
Extant Species ◽  
Central Carbon

As the core component of cell metabolism, central carbon metabolism, consisting of glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle converts nutrients into metabolic precursors for biomass and energy to sustain the life of virtually all extant species. The metabolite levels or distributions in central carbon metabolism often change dynamically with cell fates, development, and disease progression. However, traditional biochemical methods require cell lysis, making it challenging to obtain spatiotemporal information about metabolites in living cells and in vivo. Genetically encoded fluorescent sensors allow the rapid, sensitive, specific, and real-time readout of metabolite dynamics in living organisms, thereby offering the potential to fill the gap in current techniques. In this review, we introduce recent progress made in the development of genetically encoded fluorescent sensors for central carbon metabolism and discuss their advantages, disadvantages, and applications. Moreover, several future directions of metabolite sensors are also proposed.

scholarly journals Evidence for loss and reacquisition of alcoholic fermentation in a fructophilic yeast lineage

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Carla Gonçalves ◽  
Jennifer H Wisecaver ◽  
Jacek Kominek ◽  
Madalena Salema Oom ◽  
Maria José Leandro ◽  
...  
Keyword(s):  
Carbon Metabolism ◽  
Alcoholic Fermentation ◽  
Carbon Sources ◽  
Central Carbon Metabolism ◽  
Yeast Gene ◽  
Ample Evidence ◽  
High Sugar ◽  
Central Carbon ◽  
Bacterial Genes ◽  
Horizontal Acquisition

Fructophily is a rare trait that consists of the preference for fructose over other carbon sources. Here, we show that in a yeast lineage (the Wickerhamiella/Starmerella, W/S clade) comprised of fructophilic species thriving in the high-sugar floral niche, the acquisition of fructophily is concurrent with a wider remodeling of central carbon metabolism. Coupling comparative genomics with biochemical and genetic approaches, we gathered ample evidence for the loss of alcoholic fermentation in an ancestor of the W/S clade and subsequent reinstatement through either horizontal acquisition of homologous bacterial genes or modification of a pre-existing yeast gene. An enzyme required for sucrose assimilation was also acquired from bacteria, suggesting that the genetic novelties identified in the W/S clade may be related to adaptation to the high-sugar environment. This work shows how even central carbon metabolism can be remodeled by a surge of HGT events.

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