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Revisiting antibiotic resistance: mechanistic foundations to evolutionary outlook
Antibiotics are the pivotal pillar of contemporary healthcare and have contributed towards its
advancement over the decades. Antibiotic resistance emerged as a critical warning to public …
advancement over the decades. Antibiotic resistance emerged as a critical warning to public …
Epistasis and intramolecular networks in protein evolution
Proteins are molecular machines composed of complex, highly connected amino acid
networks. Their functional optimization requires the reorganization of these intramolecular …
networks. Their functional optimization requires the reorganization of these intramolecular …
A rugged yet easily navigable fitness landscape
Fitness landscape theory predicts that rugged landscapes with multiple peaks impair
Darwinian evolution, but experimental evidence is limited. In this study, we used genome …
Darwinian evolution, but experimental evidence is limited. In this study, we used genome …
The simplicity of protein sequence-function relationships
How complex are the rules by which a protein's sequence determines its function? High-
order epistatic interactions among residues are thought to be pervasive, suggesting an …
order epistatic interactions among residues are thought to be pervasive, suggesting an …
Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase
Epistasis, the non-additive effect of mutations, can provide combinatorial improvements to
enzyme activity that substantially exceed the gains from individual mutations. Yet the …
enzyme activity that substantially exceed the gains from individual mutations. Yet the …
Metabolic fitness landscapes predict the evolution of antibiotic resistance
Bacteria evolve resistance to antibiotics by a multitude of mechanisms. A central, yet
unsolved question is how resistance evolution affects cell growth at different drug levels …
unsolved question is how resistance evolution affects cell growth at different drug levels …
Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution
Enzyme evolution is characterized by constant alterations of the intramolecular residue
networks supporting their functions. The rewiring of these network interactions can give rise …
networks supporting their functions. The rewiring of these network interactions can give rise …
A trimethoprim derivative impedes antibiotic resistance evolution
MS Manna, YT Tamer, I Gaszek, N Poulides… - Nature …, 2021 - nature.com
The antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but
its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory …
its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory …
High-throughput functional variant screens via in vivo production of single-stranded DNA
Creating and characterizing individual genetic variants remains limited in scale, compared
to the tremendous variation both existing in nature and envisioned by genome engineers …
to the tremendous variation both existing in nature and envisioned by genome engineers …
Robust genetic codes enhance protein evolvability
The standard genetic code defines the rules of translation for nearly every life form on Earth.
It also determines the amino acid changes accessible via single-nucleotide mutations, thus …
It also determines the amino acid changes accessible via single-nucleotide mutations, thus …