
Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 27, P. 1 - 9
Published: Dec. 6, 2024
Language: Английский
Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 27, P. 1 - 9
Published: Dec. 6, 2024
Language: Английский
Proceedings of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 291(2016)
Published: Feb. 14, 2024
Populations declining toward extinction can persist via genetic adaptation in a process called evolutionary rescue. Predicting rescue has applications ranging from conservation biology to medicine, but requires understanding and integrating the multiple effects of stressful environmental change on population processes. Here we derive simple expression for how generation time, key determinant rate evolution, varies with size during Change time is quantitatively predicted by comparing intraspecific competition source maladaptation each affect rates births deaths population. Depending difference between two parameters quantifying these effects, model predicts that populations may experience substantial changes their both positive negative directions, or adapt consistently despite severe stress. These predictions were then tested comparison results individual-based simulations rescue, which validated tolerable varied considerably as described analytical results. We discuss inform efforts understand wildlife disease climate change, evolution managed treatment resistance pathogens.
Language: Английский
Citations
4PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(4), P. e1012861 - e1012861
Published: April 3, 2025
Bacterial populations often have complex spatial structures, which can impact their evolution. Here, we study how structure affects the evolution of antibiotic resistance in a bacterial population. We consider minimal model spatially structured where all demes (i.e., subpopulations) are identical and connected to each other by migration rates. show that facilitate survival population treatment, starting from sensitive inoculum. Specifically, be rescued if resistant mutants appear present when drug is added, fate these probability they present. Indeed, fixation neutral or deleterious mutations providing increased smaller populations. This promotes local population, facilitates evolutionary rescue rare mutation regime. Once resistance, migrations allow spread demes. Our main result extends more case there
Language: Английский
Citations
0Evolution Letters, Journal Year: 2024, Volume and Issue: 8(4), P. 587 - 599
Published: April 20, 2024
Abstract One of the longstanding puzzles antimicrobial resistance is why frequency persists at intermediate levels. Theoretical explanations for lack fixation include cryptic costs or negative frequency-dependence but are seldom explored experimentally. β-lactamases, which detoxify penicillin-related antibiotics, have well-characterized frequency-dependent dynamics driven by cheating and cooperation. However, bacterial physiology determines whether β-lactamases cooperative, we know little about sociality fitness β-lactamase producers in infections. Moreover, media-based experiments constrain how measure ignore important parameters such as infectivity transmission among hosts. Here, investigated effects broad-spectrum AmpC Enterobacter cloacae broth, biofilms, gut infections a model insect. We quantified frequency- dose-dependent using cefotaxime, third-generation cephalosporin. predicted that infection would be similar to those observed with social protection extending over wide dose range. found evidence all contexts selection, ensuring persistence wild-type bacteria, although cooperation was less prevalent contrary predictions. While competitive broth had dynamics, incorporating into measurements significantly affected conclusions. Resistant bacteria reduced infectivity, limited benefits challenged low antibiotic doses initial frequencies resistance. The resistant more physiologically tolerant states (in infections) could constrained presence high doses, availability β-lactamases. conclusion increased tolerance β-lactams does not necessarily increase selection pressure Overall, both dependence curtailed this study.
Language: Английский
Citations
2bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: May 6, 2024
Abstract Given the ongoing antimicrobial resistance crisis, it is imperative to develop dosing regimens optimised for avoiding evolution of resistance. The rate at which bacteria acquire resistance-conferring mutations different drugs spans multiple orders magnitude. By using a mathematical model and computer simulations, we show that knowledge relative mutation rates can meaningfully inform optimal combination two in treatment regimen. We demonstrate under plausible assumptions there linear relationship log-log space between drug A :drug B dose ratio maximises chance success their rates. This power law holds bacteriostatic bactericidal drugs. If borne out empirically, these findings suggest might be significant room further optimise strategies.
Language: Английский
Citations
2Journal of Basic Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 15, 2024
Antibiotic resistance is one of the major health threat for humans, animals, and environment, according to World Health Organization (WHO) Global Antibiotic-Resistance Surveillance System (GLASS). In last several years, wastewater/sewage has been identified as potential hotspots dissemination antibiotic transfer genes. However, systematic approaches mapping situation in sewage are limited underdeveloped. The present review highlighted all possible perspectives by which dynamics ARBs/ARGs environment may be tracked, quantified assessed spatio-temporally through surveillance wastewater. Moreover, application advanced methods like wastewater metagenomics determining community distribution at large appeared promising. addition, monitoring pollution various levels, serve an early warning system enable policymakers take timely measures build infrastructure mitigate crises. Thus, understanding alarming presence wastewater, effective action plans developed address this global challenge its associated environmental risks.
Language: Английский
Citations
2Evolutionary Applications, Journal Year: 2024, Volume and Issue: 17(8)
Published: Aug. 1, 2024
In combination therapy, bacteria are challenged with two or more antibiotics simultaneously. Ideally, separate mutations required to adapt each of them, which is a priori expected hinder the evolution full resistance. Yet, success this strategy ultimately depends on how well controls growth and without resistance mutations. To design treatment, we need choose drugs their doses decide many get mixed. Which combinations good? answer question, set up stochastic pharmacodynamic model determine probability successfully eradicate bacterial population. We consider bacteriostatic types bactericidal drugs-those that kill independent replication those during replication. establish results for null model, non-interacting implement most common models drug independence-Loewe additivity Bliss independence. Our show therapy almost always better in limiting than administering just one drug, even though keep total dose constant 'fair' comparison. exceptions exist steep dose-response curves. Combining can non-replicating cells particularly beneficial. suggest 50:50 ratio-even if not optimal-is usually good safe choice. Applying three four beneficial treatment strains large mutation rates but adding otherwise only provides marginal benefit disadvantage. By systematically addressing key elements design, our study basis future take further factors into account. It also highlights conceptual challenges translating traditional concepts independence single-cell level.
Language: Английский
Citations
1bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 3, 2024
Abstract Bacterial populations often have complex spatial structures, which can impact their evolution. Here, we study how structure affects the evolution of antibiotic resistance in a bacterial population. We consider minimal model spatially structured where all demes (i.e., subpopulations) are identical and connected to each other by migration rates. show that facilitate survival population treatment, starting from sensitive inoculum. Indeed, be rescued if resistant mutants appear present when drug is added, fate these probability they present. Specifically, mutation provides neutral or effectively neutral, its fixation increased smaller populations. This promotes local population, facilitates evolutionary rescue cost-free resistance. Once resistance, migrations allow spread demes. Our main results extend case there inoculum, more structures. They also carry fitness cost, although timescales involved longer. Author Summary Antibiotic major challenge, since bacteria tend adapt drugs subjected to. Understanding what conditions hinder appearance thus strong interest. Most natural microbial includes host-associated microbiota, such as gut microbiota. promoting presence bacteria. giving take over small easily than large ones, thanks importance fluctuations Resistant then whole Thus, source treatment failure. effect generic does not require environment heterogeneity.
Language: Английский
Citations
1npj Antimicrobials and Resistance, Journal Year: 2024, Volume and Issue: 2(1)
Published: Dec. 12, 2024
Exploring the dynamics and molecular mechanisms of antimicrobial drug resistance provides critical insights for developing effective strategies to combat it. This review highlights potential experimental evolution methods study in pathogenic fungi, drawing on from bacteriology innovative approaches mycology. We emphasize versatility replicating clinical environmental scenarios propose that incorporating evolutionary modelling can enhance our understanding antifungal evolution. advocate a broader application medical mycology improve still limited fungi.
Language: Английский
Citations
1Current Opinion in Microbiology, Journal Year: 2024, Volume and Issue: 82, P. 102542 - 102542
Published: Sept. 19, 2024
Language: Английский
Citations
0Journal of Mass Spectrometry and Advances in the Clinical Lab, Journal Year: 2024, Volume and Issue: 34, P. 46 - 54
Published: Nov. 1, 2024
Language: Английский
Citations
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