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dc.contributor.authorRossi, O
dc.contributor.authorDybowski, R
dc.contributor.authorMaskell, DJ
dc.contributor.authorGrant, AJ
dc.contributor.authorRestif, O
dc.contributor.authorMastroeni, P
dc.date.accessioned2017-07-28T15:13:24Z
dc.date.available2017-07-28T15:13:24Z
dc.date.issued2017-08-23
dc.identifier.issn0305-7453
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265775
dc.description.abstract$\textbf{Objectives:}$ We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic $\textit{Salmonella}$ infections. $\textbf{Methods:}$ We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing $\Delta$$\textit{aroC Salmonella}$ strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin. $\textbf{Results:}$ Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment. $\textbf{Conclusions:}$ In $\textit{Salmonella}$ infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.
dc.description.sponsorshipThis work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/M000982/1 (http://www.bbsrc.ac.uk/research/grants/grants/AwardDetails.aspx?FundingReference=BB/M000982/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.language.isoen
dc.publisherOxford University Press
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleWithin-host spatiotemporal dynamics of systemic Salmonella infection during and after antimicrobial treatment
dc.typeArticle
prism.publicationDate2017
prism.publicationNameJournal of Antimicrobial Chemotherapy
dc.identifier.doi10.17863/CAM.11965
dcterms.dateAccepted2017-07-20
rioxxterms.versionofrecord10.1093/jac/dkx294
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2017-08-23
dc.contributor.orcidRossi, Omar [0000-0001-8492-2472]
dc.contributor.orcidMaskell, Duncan [0000-0002-5065-653X]
dc.contributor.orcidGrant, Andrew [0000-0001-9746-2989]
dc.contributor.orcidRestif, Olivier [0000-0001-9158-853X]
dc.contributor.orcidMastroeni, Pietro [0000-0003-3838-4962]
dc.identifier.eissn1460-2091
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/M000982/1)
cam.issuedOnline2017-08-23
cam.orpheus.successThu Jan 30 12:53:29 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International