ArticleProceedings of the National Academy of Sciences of the United States of America2022
Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone resistance evolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Evolutionary drivers of divergent collateral sensitivity responses during antibiotic therapy.Nature ecology & evolution · 2026Review
- Collateral effects of antibiotic resistance in Campylobacter jejuni.FEMS microbiology letters · 2026Article
- Invariant set theory for predicting potential failure of antibiotic cycling.Infectious Disease Modelling · 2025Article
- Collateral sensitivity and cross-resistance in six species of bacteria exposed to six classes of antibiotics.Microbiology spectrum · 2025Article
- Article
- Preserving the efficacy of antibiotics to tackle antibiotic resistance.Microbial biotechnology · 2024Review
- Heterogeneous Phenotypic Responses of Antibiotic-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Translating eco-evolutionary biology into therapy to tackle antibiotic resistance.Nature reviews. Microbiology · 2023Review
- Pervasive genotype-by-environment interactions shape the fitness effects of antibiotic resistance mutations.Proceedings. Biological sciences · 2023Article
- Ciprofloxacin and Tetracycline Resistance Cause Collateral Sensitivity to Aminoglycosides inAntibiotics (Basel, Switzerland) · 2023Article
- The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis.Nature communications · 2023Article
- Variability in Adaptive Resistance ofAntibiotics (Basel, Switzerland) · 2022Article
- Article
- Identification of antibiotic collateral sensitivity and resistance interactions in population surveillance data.JAC-antimicrobial resistance · 2021Article
- Design principles of collateral sensitivity-based dosing strategies.Nature communications · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collateral sensitivity (CS), which arises when resistance to one antibiotic increases sensitivity toward other antibiotics, offers treatment opportunities to constrain or reverse the evolution of antibiotic resistance. The applicability of CS-informed treatments remains uncertain, in part because we lack an understanding of the generality of CS effects for different resistance mutations, singly or in combination. Here, we address this issue in the gram-positive pathogen Streptococcus pneumoniae by measuring collateral and fitness effects of clinically relevant gyrA and parC alleles and their combinations that confer resistance to fluoroquinolones. We integrated these results in a mathematical model that allowed us to evaluate how different in silico combination treatments impact the dynamics of resistance evolution. We identified common and conserved CS effects of different gyrA and parC alleles; however, the spectrum of collateral effects was unique for each allele or allelic pair. This indicated that allelic identity can impact the evolutionary dynamics of resistance evolution during monotreatment and combination treatment. Our model simulations, which included the experimentally derived antibiotic susceptibilities and fitness effects, and antibiotic-specific pharmacodynamics revealed that both collateral and fitness effects impact the population dynamics of resistance evolution. Overall, we provide evidence that allelic identity and interactions can have a pronounced impact on collateral effects to different antibiotics and suggest that these need to be considered in models examining CS-based therapies.
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