Revisiting antibiotic resistance: mechanistic foundations to evolutionary outlook

CM Hasan, D Dutta, ANT Nguyen - Antibiotics, 2021 - mdpi.com
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 …

Epistasis and intramolecular networks in protein evolution

CM Miton, K Buda, N Tokuriki - Current opinion in structural biology, 2021 - Elsevier
Proteins are molecular machines composed of complex, highly connected amino acid
networks. Their functional optimization requires the reorganization of these intramolecular …

A rugged yet easily navigable fitness landscape

A Papkou, L Garcia-Pastor, JA Escudero, A Wagner - Science, 2023 - science.org
Fitness landscape theory predicts that rugged landscapes with multiple peaks impair
Darwinian evolution, but experimental evidence is limited. In this study, we used genome …

The simplicity of protein sequence-function relationships

Y Park, BPH Metzger, JW Thornton - Nature Communications, 2024 - nature.com
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 …

Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase

C Fröhlich, HA Bunzel, K Buda, AJ Mulholland… - Nature Catalysis, 2024 - nature.com
Epistasis, the non-additive effect of mutations, can provide combinatorial improvements to
enzyme activity that substantially exceed the gains from individual mutations. Yet the …

Metabolic fitness landscapes predict the evolution of antibiotic resistance

F Pinheiro, O Warsi, DI Andersson… - Nature Ecology & …, 2021 - nature.com
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 …

Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution

K Buda, CM Miton, N Tokuriki - Nature Communications, 2023 - nature.com
Enzyme evolution is characterized by constant alterations of the intramolecular residue
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 …

High-throughput functional variant screens via in vivo production of single-stranded DNA

MG Schubert, DB Goodman, TM Wannier… - Proceedings of the …, 2021 - pnas.org
Creating and characterizing individual genetic variants remains limited in scale, compared
to the tremendous variation both existing in nature and envisioned by genome engineers …

Robust genetic codes enhance protein evolvability

H Rozhoňová, C Martí-Gómez, DM McCandlish… - PLoS …, 2024 - journals.plos.org
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 …