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7 results for “Collateral evolution”
Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone-resistance evolution
<p>Collateral sensitivity (CS), which arises when resistance to one antibiotic increases sensitivity towards other antibiotics, offers novel 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 <em>Streptococcus</em> <em>pneumoniae</em> by measuring collateral and fitness effects of clinically relevant <em>gyrA</em> and <em>parC</em> alleles, and their combinations, that confer resistance to fluoroquinolones. We integrated these results in a mathematical model which allowed us to evaluate how different <em>in</em> <em>silico</em> combination treatments impact the dynamics of resistance evolution. We identified common and conserved CS effects of different <em>gyrA</em> and <em>parC</em> 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 of different antibiotics and suggest that these need to be considered in models examining CS-based therapies.</p>
Allele-specific collateral and fitness effects determine the dynamics of fluoroquinolone-resistance evolution
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Evolution under vancomycin selection drives divergent collateral sensitivity patterns in <em>Staphylococcus aureus</em>
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Data from: Macrophage adaptation leads to parallel evolution of genetically diverse Escherichia coli small-colony variants with increased fitness in vivo and antibiotic collateral sensitivity
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Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas.
GEO Series GSE298261. Homo sapiens. 20 samples. Type: Expression profiling by high throughput sequencing.
Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution
GEO Series GSE72910. Mus musculus. 10 samples. Type: Expression profiling by high throughput sequencing.
Phenotypic convergent evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic resistant mutants
GEO Series GSE153006. Pseudomonas aeruginosa. 5 samples. Type: Expression profiling by high throughput sequencing.
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