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Within-host spatiotemporal dynamics of systemic Salmonella infection during and after antimicrobial treatment

Accepted version
Peer-reviewed

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Authors

Dybowski, R 
Maskell, DJ 
Grant, AJ 

Abstract

Objectives: We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic Salmonella infections.

Methods: We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing ΔaroC 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.

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.

Conclusions: In 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.

Description

Keywords

Ampicillin, Animal Structures, Animals, Anti-Bacterial Agents, Bacterial Load, Blood, Ciprofloxacin, Disease Models, Animal, Female, Mice, Inbred C57BL, Salmonella, Salmonella Infections, Sepsis, Spatio-Temporal Analysis

Journal Title

Journal of Antimicrobial Chemotherapy

Conference Name

Journal ISSN

0305-7453
1460-2091

Volume Title

Publisher

Oxford University Press
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M000982/1)
This 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.