Utilization of host polyamines in alternatively activated macrophages promotes chronic infection byBrucella abortus.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621323
Title:
Utilization of host polyamines in alternatively activated macrophages promotes chronic infection byBrucella abortus.
Authors:
Kerrinnes, Tobias; Winter, Maria G; Young, Briana M; Diaz-Ochoa, Vladimir E; Winter, Sebastian E; Tsolis, Renée M
Abstract:
Treatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple antibiotics. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogenBrucella abortussurvives and replicates preferentially in alternatively activated macrophages (AAM), however knowledge of the metabolic adaptations promoting exploitation of this niche is limited. Here we show that one mechanism promoting enhanced survival in AAM is a shift in macrophage arginine utilization from production of nitric oxide (NO) to biosynthesis of polyamines, induced by IL-4/IL-13 treatment.B. abortusis unable to synthesize polyamines, however production of polyamines by infected AAM promoted both intracellular survival of bacteria and chronic infection in mice, as inhibition of macrophage polyamine synthesis or inactivation of theB. abortusputrescine transporterpotIHGFreduced both intracellular survival in AAM and persistence in mice. These results demonstrate that increased intracellular availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced AAM promotes chronic persistence ofB. abortuswithin this niche and suggest that targeting of this pathway may aid in eradicating chronic infection.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Utilization of host polyamines in alternatively activated macrophages promotes chronic infection byBrucella abortus. 2017 Infect. Immun.
Journal:
Infection and immunity
Issue Date:
4-Dec-2017
URI:
http://hdl.handle.net/10033/621323
DOI:
10.1128/IAI.00458-17
PubMed ID:
29203548
Type:
Article
Language:
en
ISSN:
1098-5522
Appears in Collections:
Publications of the department of epidemiology (EPID)

Full metadata record

DC FieldValue Language
dc.contributor.authorKerrinnes, Tobiasen
dc.contributor.authorWinter, Maria Gen
dc.contributor.authorYoung, Briana Men
dc.contributor.authorDiaz-Ochoa, Vladimir Een
dc.contributor.authorWinter, Sebastian Een
dc.contributor.authorTsolis, Renée Men
dc.date.accessioned2018-03-16T14:20:29Z-
dc.date.available2018-03-16T14:20:29Z-
dc.date.issued2017-12-04-
dc.identifier.citationUtilization of host polyamines in alternatively activated macrophages promotes chronic infection byBrucella abortus. 2017 Infect. Immun.en
dc.identifier.issn1098-5522-
dc.identifier.pmid29203548-
dc.identifier.doi10.1128/IAI.00458-17-
dc.identifier.urihttp://hdl.handle.net/10033/621323-
dc.description.abstractTreatment of intracellular bacterial pathogens with antibiotic therapy often requires a long course of multiple antibiotics. A barrier to developing strategies that enhance antibiotic efficacy against these pathogens is our poor understanding of the intracellular nutritional environment that maintains bacterial persistence. The intracellular pathogenBrucella abortussurvives and replicates preferentially in alternatively activated macrophages (AAM), however knowledge of the metabolic adaptations promoting exploitation of this niche is limited. Here we show that one mechanism promoting enhanced survival in AAM is a shift in macrophage arginine utilization from production of nitric oxide (NO) to biosynthesis of polyamines, induced by IL-4/IL-13 treatment.B. abortusis unable to synthesize polyamines, however production of polyamines by infected AAM promoted both intracellular survival of bacteria and chronic infection in mice, as inhibition of macrophage polyamine synthesis or inactivation of theB. abortusputrescine transporterpotIHGFreduced both intracellular survival in AAM and persistence in mice. These results demonstrate that increased intracellular availability of polyamines induced by arginase-1 expression in IL-4/IL-13-induced AAM promotes chronic persistence ofB. abortuswithin this niche and suggest that targeting of this pathway may aid in eradicating chronic infection.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleUtilization of host polyamines in alternatively activated macrophages promotes chronic infection byBrucella abortus.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalInfection and immunityen

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