Related papers: Development of antibacterial compounds that block …
Genetic inactivation of essential genes creates an evolutionary scenario distinct from escape from drug inhibition, but the mechanisms of microbe adaptations in such cases remain unknown. Here we inactivate E. coli dihydrofolate reductase…
Diseases caused by bacteria have been a threat to human civilisation for centuries. Despite the availability of numerous antibacterial drugs today, bacterial diseases continue to pose life-threatening challenges. The credit for this goes to…
The evolution of antibiotic resistance among bacteria threatens our continued ability to treat infectious diseases. The need for sustainable strategies to cure bacterial infections has never been greater. So far, all attempts to restore…
Serine hydroxymethyltransferase is an essential enzyme in the Escherichia coli folate pathway, yet it has not been adopted as an antibacterial target, unlike DHFR, DHPS, or thymidylate synthase. To investigate this discrepancy, we applied a…
Bacteria pose unique challenges for genome-wide association studies (GWAS) because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome. While methods developed for human studies can correct…
The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical…
Due to the rise in antimicrobial resistance, identifying novel compounds with antibiotic potential is crucial for combatting this global health issue. However, traditional drug development methods are costly and inefficient. Recognizing the…
The development of reliable methods for restoring susceptibility after antibiotic resistance arises has proven elusive. A greater understanding of the relationship between antibiotic administration and the evolution of resistance is key to…
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. Here we develop a fitness model that predicts growth rates of…
High-throughput molecular screening is required to investigate the origin and diffusion of antimicrobial resistance in pathogen outbreaks. The most frequent cause of human infection is Escherichia coli, which is dominated by sequence type…
Antibiotic resistance presents a growing global health crisis, demanding new therapeutic strategies that target novel bacterial mechanisms. Recent advances in protein structure prediction and machine learning-driven molecule generation…
Antimicrobial resistance is an emerging global health crisis that is undermining advances in modern medicine and, if unmitigated, threatens to kill 10 million people per year worldwide by 2050. Research over the last decade has demonstrated…
Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anti-cancer drugs. We use a statistical physics model to study the evolution of a population of malignant…
Bacteria develop resistance to antibiotics through various mechanisms, with the specific mechanism depending on the drug-bacteria pair. It remains unclear, however, which resistance mechanism best supports favorable treatment outcomes,…
Antibiotic resistance is a growing public health problem. To gain a fundamental understanding of resistance evolution, a combination of systematic experimental and theoretical approaches is required. Evolution experiments combined with…
Non-genetic forms of antimicrobial drug resistance can result from cell-to-cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non-genetic mechanisms can facilitate the development of…
As part of a program to develop compounds with potential to treat cocaine abuse, eleven (+/-)-threo-methylphenidate (TMP; Ritalin) derivatives were synthesized and tested in rat striatal tissue preparations for inhibitory potency against…
De novo therapeutic design is challenged by a vast chemical repertoire and multiple constraints, e.g., high broad-spectrum potency and low toxicity. We propose CLaSS (Controlled Latent attribute Space Sampling) - an efficient computational…
Antimicrobial resistance is becoming a major threat to public health throughout the world. Researchers are attempting to contrast it by developing both new antibiotics and patient-specific treatments. In the second case, whole-genome…
Drug resistance is a serious public health problem that threatens to thwart our ability to treat many infectious diseases. Repeatedly, the introduction of new drugs has been followed by the evolution of resistance. In principle there are…