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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients
Julio Diaz Caballero1, Rachel M Wheatley1, Natalia Kapel1
1University of Oxford, Department of Biology, 11a Mansfield Rd, Oxford, UK.
Abstract:
Antibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogen P. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.
Insights
Antibiotic resistance evolves faster in patients with mixed pathogen strains due to selection of pre-existing resistance. Within-host diversity also drives resistance loss when antibiotics are absent.
Area of Science:
- Microbiology
- Evolutionary Biology
- Clinical Medicine
Background:
- Antibiotic resistance is a major global health concern.
- Understanding within-host pathogen evolution is crucial for effective treatment.
- Pathogen populations are often assumed to be clonal within hosts.
Purpose of the Study:
- To investigate the role of within-host pathogen diversity in the emergence of antibiotic resistance.
- To compare resistance evolution in single-strain versus mixed-strain infections.
- To explore the impact of within-host diversity on resistance dynamics.
Main Methods:
- Studied the opportunistic pathogen Pseudomonas aeruginosa.
- Analyzed pathogen populations within patients.
- Compared resistance evolution in single-strain and mixed-strain colonization.
Main Results:
- Mixed-strain populations of P. aeruginosa are common within hosts.
- Rapid resistance evolution occurs in mixed-strain infections via selection of pre-existing resistant strains.
- Sporadic resistance evolution in single-strain infections results from selection for novel mutations.
- Strong trade-offs between resistance and growth rate in mixed strains can lead to resistance loss without antibiotics.
Conclusions:
- Within-host pathogen diversity significantly influences the emergence and loss of antibiotic resistance.
- Mixed-strain infections accelerate resistance evolution compared to single-strain infections.
- Within-host diversity has a dual role, promoting resistance emergence under antibiotic pressure and loss in its absence.
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