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Virulence of antibiotic-resistant Salmonella typhimurium
J Björkman1, D Hughes, D I Andersson
1Swedish Institute for Infectious Disease Control, S-10521, Stockholm, Sweden.
Abstract:
We show that most Salmonella typhimurium mutants resistant to streptomycin, rifampicin, and nalidixic acid are avirulent in mice. Of seven resistant mutants examined, six were avirulent and one was similar to the wild type in competition experiments in mice. The avirulent-resistant mutants rapidly accumulated various types of compensatory mutations that restored virulence without concomitant loss of resistance. Such second-site compensatory mutations were more common then reversion to the sensitive wild type. We infer from these results that a reduction in the use of antibiotics might not result in the disappearance of the resistant bacteria already present in human and environmental reservoirs. Thus, second-site compensatory mutations could increase the fitness of resistant bacteria and allow them to persist and compete successfully with sensitive strains even in an antibiotic-free environment.
Insights
Most antibiotic-resistant Salmonella typhimurium mutants are not virulent in mice. Compensatory mutations can restore virulence, allowing resistant bacteria to persist even without antibiotic use.
Area of Science:
- Microbiology
- Genetics
- Evolutionary Biology
Background:
- Antibiotic resistance in bacteria poses a significant public health threat.
- The fitness and persistence of resistant bacterial strains in the absence of antibiotics are not fully understood.
Purpose of the Study:
- To investigate the virulence and evolutionary potential of Salmonella typhimurium mutants resistant to multiple antibiotics.
- To determine if compensatory mutations can restore virulence in resistant strains.
Main Methods:
- Generation of Salmonella typhimurium mutants resistant to streptomycin, rifampicin, and nalidixic acid.
- Assessment of bacterial virulence through competition experiments in a mouse model.
- Genomic analysis to identify compensatory mutations.
Main Results:
- Most antibiotic-resistant Salmonella typhimurium mutants examined were avirulent in mice.
- Avirulent-resistant mutants acquired second-site compensatory mutations that restored virulence without losing antibiotic resistance.
- Compensatory mutations were more frequent than reversion to antibiotic sensitivity.
Conclusions:
- Antibiotic resistance can be maintained in bacterial populations through compensatory mutations that restore fitness.
- Reduced antibiotic use may not eliminate resistant bacteria from reservoirs due to compensatory evolution.
- Resistant bacteria with restored fitness can persist and compete with sensitive strains in antibiotic-free environments.