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2018-10-22Zeitschriftenartikel DOI: 10.25646/6041
Bringing together what belongs together: Optimizing murine infection models by using mouse-adapted Staphylococcus aureus strains
dc.contributor.authorTrübe, Patricia
dc.contributor.authorHertlein, Tobias
dc.contributor.authorMrochen, Daniel M.
dc.contributor.authorSchulz, Daniel
dc.contributor.authorJorde, Ilka
dc.contributor.authorKrause, Bettina
dc.contributor.authorZeun, Julia
dc.contributor.authorFischer, Stefan
dc.contributor.authorWolf, Silver A.
dc.contributor.authorWalther, Birgit
dc.contributor.authorSemmler, Torsten
dc.contributor.authorBröker, Barbara M.
dc.contributor.authorUlrich, Rainer G.
dc.contributor.authorOhlsen, Knut
dc.contributor.authorHoltfreter, Silva
dc.date.accessioned2019-03-29T12:43:29Z
dc.date.available2019-03-29T12:43:29Z
dc.date.issued2018-10-22none
dc.identifier.other10.1016/j.ijmm.2018.10.007
dc.identifier.urihttp://edoc.rki.de/176904/6076
dc.description.abstractStaphylococcus (S.) aureus is a leading cause of bacterial infection world-wide, and currently no vaccine is available for humans. Vaccine development relies heavily on clinically relevant infection models. However, the suitability of mice for S. aureus infection models has often been questioned, because experimental infection of mice with human-adapted S. aureus requires very high infection doses. Moreover, mice were not considered to be natural hosts of S. aureus. The latter has been disproven by our recent findings, showing that both laboratory mice, as well as wild small mammals including mice, voles, and shrews, are naturally colonized with S. aureus. Here, we investigated whether mouse-and vole-derived S. aureus strains show an enhanced virulence in mice as compared to the human-adapted strain Newman. Using a step-wise approach based on the bacterial genotype and in vitro assays for host adaptation, we selected the most promising candidates for murine infection models out of a total of 254 S. aureus isolates from laboratory mice as well as wild rodents and shrews. Four strains representing the clonal complexes (CC) 8, 49, and 88 (n = 2) were selected and compared to the human-adapted S. aureus strain Newman (CC8) in murine pneumonia and bacteremia models. Notably, a bank vole-derived CC49 strain, named DIP, was highly virulent in BALB/c mice in pneumonia and bacteremia models, whereas the other murine and vole strains showed virulence similar to or lower than that of Newman. At one tenth of the standard infection dose DIP induced disease severity, bacterial load and host cytokine and chemokine responses in the murine bacteremia model similar to that of Newman. In the pneumonia model, DIP was also more virulent than Newman but the effect was less pronounced. Whole genome sequencing data analysis identified a pore-forming toxin gene, lukF-PV(P83)/lukM, in DIP but not in the other tested S. aureus isolates. To conclude, the mouse-adapted S. aureus strain DIP allows a significant reduction of the inoculation dose in mice and is hence a promising tool to develop clinically more relevant infection models.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectStaphylococcus aureuseng
dc.subjectHost-adaptedeng
dc.subjectInfection modeleng
dc.subjectMouseeng
dc.subjectVoleeng
dc.subjectCC49eng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleBringing together what belongs together: Optimizing murine infection models by using mouse-adapted Staphylococcus aureus strainsnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:0257-176904/6076-3
dc.identifier.doihttp://dx.doi.org/10.25646/6041
dc.type.versionpublishedVersionnone
local.edoc.container-titleInternational Journal of Medical Microbiologynone
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.sciencedirect.com/science/article/pii/S1438422118302121?via%3Dihubnone
local.edoc.container-publisher-nameElseviernone
local.edoc.container-volume1none
local.edoc.container-issueJanuary 2019none
local.edoc.container-reportyear2018none
local.edoc.container-year2018none
local.edoc.container-firstpage26none
local.edoc.container-lastpage38none
local.edoc.rki-departmentProjektgruppen/Nachwuchsgruppennone
dc.description.versionPeer Reviewednone

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