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Updated: Jul 24, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Within-host spatiotemporal dynamics of systemic Salmonella infection during and after antimicrobial treatment
O Rossi1, R Dybowski1, D J Maskell1
1University of Cambridge, Department of Veterinary Medicine, Cambridge, UK.
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.
Insights
Bacterial growth rates impact antibiotic effectiveness in Salmonella infections. Mesenteric lymph nodes (MLNs) harbor distinct bacterial populations resistant to treatment and prone to relapse.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Systemic Salmonella infections pose significant health risks.
- Understanding antibiotic treatment dynamics is crucial for effective management.
- Pathogen growth rates and organ-specific dissemination influence treatment outcomes.
Purpose of the Study:
- To investigate the interplay between antibiotic efficacy, pathogen growth rates, and inter-organ spread in systemic Salmonella infections.
- To determine how bacterial growth kinetics affect antimicrobial treatment outcomes in vivo.
Main Methods:
- Mice were infected with isogenic, molecularly tagged subpopulations of either fast-growing wild-type (WT) or slow-growing ΔaroC Salmonella.
- Bacterial loads and subpopulation proportions were monitored in spleen, liver, blood, and mesenteric lymph nodes (MLNs).
- Monitoring occurred before, during, and after treatment with ampicillin and ciprofloxacin.
Main Results:
- Both antibiotics reduced bacterial numbers in spleen, liver, and blood, with efficacy correlating positively with Salmonella growth rates.
- Fast-growing bacteria showed a biphasic reduction, while slow-growing bacteria exhibited a gradual decrease in bacterial load.
- Bacterial numbers in MLNs remained constant during treatment, showing distinct population structures compared to spleen and liver.
- Infections relapsed in MLNs after treatment cessation, particularly with WT Salmonella.
Conclusions:
- Bacterial growth rates are a key determinant of antibiotic treatment efficacy in Salmonella infections.
- Mesenteric lymph nodes (MLNs) serve as a reservoir for Salmonella, with distinct bacterial population dynamics.
- Antimicrobials have limited impact on MLN bacterial loads, which can regrow post-treatment, highlighting a potential mechanism for relapse.
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