Matches in SemOpenAlex for { <https://semopenalex.org/work/W2337282573> ?p ?o ?g. }
- W2337282573 endingPage "e0137976" @default.
- W2337282573 startingPage "e0137976" @default.
- W2337282573 abstract "Leishmania infantum, causative agent of visceral leishmaniasis in humans, illustrates a complex lifecycle pertaining to two extreme environments, namely, the gut of the sandfly vector and human macrophages. Leishmania is capable of dynamically adapting and tactically switching between these critically hostile situations. The possible metabolic routes ventured by the parasite to achieve this exceptional adaptation to its varying environments are still poorly understood. In this study, we present an extensively reconstructed energy metabolism network of Leishmania infantum as an attempt to identify certain strategic metabolic routes preferred by the parasite to optimize its survival in such dynamic environments. The reconstructed network consists of 142 genes encoding for enzymes performing 237 reactions distributed across five distinct model compartments. We annotated the subcellular locations of different enzymes and their reactions on the basis of strong literature evidence and sequence-based detection of cellular localization signal within a protein sequence. To explore the diverse features of parasite metabolism the metabolic network was implemented and analyzed as a constraint-based model. Using a systems-based approach, we also put forth an extensive set of lethal reaction knockouts; some of which were validated using published data on Leishmania species. Performing a robustness analysis, the model was rigorously validated and tested for the secretion of overflow metabolites specific to Leishmania under varying extracellular oxygen uptake rate. Further, the fate of important non-essential amino acids in L. infantum metabolism was investigated. Stage-specific scenarios of L. infantum energy metabolism were incorporated in the model and key metabolic differences were outlined. Analysis of the model revealed the essentiality of glucose uptake, succinate fermentation, glutamate biosynthesis and an active TCA cycle as driving forces for parasite energy metabolism and its optimal growth. Finally, through our in silico knockout analysis, we could identify possible therapeutic targets that provide experimentally testable hypotheses." @default.
- W2337282573 created "2016-06-24" @default.
- W2337282573 creator A5017524626 @default.
- W2337282573 creator A5065716947 @default.
- W2337282573 creator A5091792722 @default.
- W2337282573 date "2015-09-14" @default.
- W2337282573 modified "2023-10-03" @default.
- W2337282573 title "Dissecting Leishmania infantum Energy Metabolism - A Systems Perspective" @default.
- W2337282573 cites W1505556779 @default.
- W2337282573 cites W1516459493 @default.
- W2337282573 cites W1908562064 @default.
- W2337282573 cites W1966394322 @default.
- W2337282573 cites W1969569801 @default.
- W2337282573 cites W1969686592 @default.
- W2337282573 cites W1972863608 @default.
- W2337282573 cites W1979080877 @default.
- W2337282573 cites W1986482900 @default.
- W2337282573 cites W1986799526 @default.
- W2337282573 cites W2003227802 @default.
- W2337282573 cites W2008282437 @default.
- W2337282573 cites W2011553235 @default.
- W2337282573 cites W2012285734 @default.
- W2337282573 cites W2016713141 @default.
- W2337282573 cites W2017699535 @default.
- W2337282573 cites W2020275611 @default.
- W2337282573 cites W2032045884 @default.
- W2337282573 cites W2032841397 @default.
- W2337282573 cites W2037284663 @default.
- W2337282573 cites W2042291896 @default.
- W2337282573 cites W2042451199 @default.
- W2337282573 cites W2043208192 @default.
- W2337282573 cites W2044935306 @default.
- W2337282573 cites W2046144222 @default.
- W2337282573 cites W2048214825 @default.
- W2337282573 cites W2057884899 @default.
- W2337282573 cites W2059953844 @default.
- W2337282573 cites W2060347174 @default.
- W2337282573 cites W2066954635 @default.
- W2337282573 cites W2071921489 @default.
- W2337282573 cites W2078355959 @default.
- W2337282573 cites W2078775934 @default.
- W2337282573 cites W2079733254 @default.
- W2337282573 cites W2081085370 @default.
- W2337282573 cites W2081275903 @default.
- W2337282573 cites W2085352255 @default.
- W2337282573 cites W2085993965 @default.
- W2337282573 cites W2089047063 @default.
- W2337282573 cites W2091788742 @default.
- W2337282573 cites W2096245011 @default.
- W2337282573 cites W2104482284 @default.
- W2337282573 cites W2105105987 @default.
- W2337282573 cites W2106576546 @default.
- W2337282573 cites W2106806321 @default.
- W2337282573 cites W2107158607 @default.
- W2337282573 cites W2109009897 @default.
- W2337282573 cites W2111973517 @default.
- W2337282573 cites W2113617378 @default.
- W2337282573 cites W2115815568 @default.
- W2337282573 cites W2116354728 @default.
- W2337282573 cites W2123377654 @default.
- W2337282573 cites W2125079066 @default.
- W2337282573 cites W2126812590 @default.
- W2337282573 cites W2128074057 @default.
- W2337282573 cites W2131848047 @default.
- W2337282573 cites W2134292511 @default.
- W2337282573 cites W2139566104 @default.
- W2337282573 cites W2140351370 @default.
- W2337282573 cites W2140442761 @default.
- W2337282573 cites W2142030561 @default.
- W2337282573 cites W2145382965 @default.
- W2337282573 cites W2147472054 @default.
- W2337282573 cites W2147526198 @default.
- W2337282573 cites W2151265156 @default.
- W2337282573 cites W2151770702 @default.
- W2337282573 cites W2156690245 @default.
- W2337282573 cites W2158842589 @default.
- W2337282573 cites W2159299078 @default.
- W2337282573 cites W2163301856 @default.
- W2337282573 cites W2171769617 @default.
- W2337282573 cites W2605068739 @default.
- W2337282573 cites W4242729757 @default.
- W2337282573 cites W56055795 @default.
- W2337282573 doi "https://doi.org/10.1371/journal.pone.0137976" @default.
- W2337282573 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4569355" @default.
- W2337282573 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26367006" @default.
- W2337282573 hasPublicationYear "2015" @default.
- W2337282573 type Work @default.
- W2337282573 sameAs 2337282573 @default.
- W2337282573 citedByCount "19" @default.
- W2337282573 countsByYear W23372825732016 @default.
- W2337282573 countsByYear W23372825732017 @default.
- W2337282573 countsByYear W23372825732018 @default.
- W2337282573 countsByYear W23372825732019 @default.
- W2337282573 countsByYear W23372825732020 @default.
- W2337282573 countsByYear W23372825732021 @default.
- W2337282573 countsByYear W23372825732022 @default.
- W2337282573 crossrefType "journal-article" @default.
- W2337282573 hasAuthorship W2337282573A5017524626 @default.