Blocks in Tricarboxylic Acid Cycle of Salmonella enterica Cause Global Perturbation of Carbon Storage, Motility, and Host-Pathogen Interaction

DC FieldValueLanguage
dc.contributor.authorNoster, Janina
dc.contributor.authorHansmeier, Nicole
dc.contributor.authorPersicke, Marcus
dc.contributor.authorChao, Tzu-Chiao
dc.contributor.authorKurre, Rainer
dc.contributor.authorPopp, Jasmin
dc.contributor.authorKrieger, Viktoria
dc.contributor.authorReuter, Tatjana
dc.contributor.authorHensel, Michael
dc.date.accessioned2021-12-23T16:14:20Z-
dc.date.available2021-12-23T16:14:20Z-
dc.date.issued2019
dc.identifier.issn23795042
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/11027-
dc.description.abstractThe tricarboxylic acid (TCA) cycle is a central metabolic hub in most cells. Virulence functions of bacterial pathogens such as facultative intracellular Salmonella enterica serovar Typhimurium (S. Typhimurium) are closely connected to cellular metabolism. During systematic analyses of mutant strains with defects in the TCA cycle, a strain deficient in all fumarase isoforms (Delta fumABC) elicited a unique metabolic profile. Alongside fumarate, S. Typhimurium Delta fumABC accumulates intermediates of the glycolysis and pentose phosphate pathway. Analyses by metabolomics and proteomics revealed that fumarate accumulation redirects carbon fluxes toward glycogen synthesis due to high (p)ppGpp levels. In addition, we observed reduced abundance of CheY, leading to altered motility and increased phagocytosis of S. Typhimurium by macrophages. Deletion of glycogen synthase restored normal carbon fluxes and phagocytosis and partially restored levels of CheY. We propose that utilization of accumulated fumarate as carbon source induces a status similar to exponential- to stationary-growth-phase transition by switching from preferred carbon sources to fumarate, which increases (p)ppGpp levels and thereby glycogen synthesis. Thus, we observed a new form of interplay between metabolism of S. Typhimurium and cellular functions and virulence. IMPORTANCE We performed perturbation analyses of the tricarboxylic acid cycle of the gastrointestinal pathogen Salmonella enterica serovar Typhimurium. The defect of fumarase activity led to accumulation of fumarate but also resulted in a global alteration of carbon fluxes, leading to increased storage of glycogen. Gross alterations were observed in proteome and metabolome compositions of fumarase-deficient Salmonella. In turn, these changes were linked to aberrant motility patterns of the mutant strain and resulted in highly increased phagocytic uptake by macrophages. Our findings indicate that basic cellular functions and specific virulence functions in Salmonella critically depend on the proper function of the primary metabolism.
dc.description.sponsorshipDFGGerman Research Foundation (DFG)European Commission; This work was supported by grants of the DFG to M.H.
dc.language.isoen
dc.publisherAMER SOC MICROBIOLOGY
dc.relation.ispartofMSPHERE
dc.subjectchemotaxis
dc.subjectDEHYDROGENASE
dc.subjectESCHERICHIA-COLI
dc.subjectFUMARATE
dc.subjectGENE-EXPRESSION
dc.subjectglycogen metabolism
dc.subjectINTEGRATION
dc.subjectINVASION
dc.subjectMECHANISM
dc.subjectMETABOLISM
dc.subjectMicrobiology
dc.subjectphagocytosis
dc.subjectPROTEIN
dc.subjectTCA cycle
dc.subjectTYPHIMURIUM
dc.titleBlocks in Tricarboxylic Acid Cycle of Salmonella enterica Cause Global Perturbation of Carbon Storage, Motility, and Host-Pathogen Interaction
dc.typejournal article
dc.identifier.doi10.1128/mSphere.00796-19
dc.identifier.isiISI:000506191700039
dc.description.volume4
dc.description.issue6
dc.contributor.orcid0000-0001-9948-9560
dc.contributor.orcid0000-0002-1304-2512
dc.contributor.orcid0000-0001-6604-6253
dc.contributor.orcid0000-0002-8802-6605
dc.publisher.place1752 N ST NW, WASHINGTON, DC 20036-2904 USA
dcterms.isPartOf.abbreviationmSphere
dcterms.oaStatusGreen Published, gold, Green Submitted
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.deptidfb05-
crisitem.author.orcid0000-0002-6872-6567-
crisitem.author.orcid0000-0001-6604-6253-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidKuRa617-
crisitem.author.netidHeMi480-
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