Microbial phenotypic heterogeneity in response to a metabolic toxin: Continuous, dynamically shifting distribution of formaldehyde tolerance in Methylobacterium extorquens populations DOI Creative Commons
Jessica A. Lee, Siavash Riazi, Shahla Nemati

и другие.

PLoS Genetics, Год журнала: 2019, Номер 15(11), С. e1008458 - e1008458

Опубликована: Ноя. 11, 2019

While microbiologists often make the simplifying assumption that genotype determines phenotype in a given environment, it is becoming increasingly apparent phenotypic heterogeneity (in which one generates multiple phenotypes simultaneously even uniform environment) common many microbial populations. The importance of has been demonstrated number model systems involving binary states (e.g., growth/non-growth); however, less known about distributions are continuous across an environmental gradient, and how those change when environment changes. Here, we describe novel instance diversity tolerance to metabolic toxin within wild-type populations Methylobacterium extorquens, ubiquitous phyllosphere methylotroph capable growing on methanol periodically released from plant leaves. first intermediate metabolism formaldehyde, potent cellular lethal high concentrations. We have found at moderate concentrations, formaldehyde M. extorquens heterogeneous, with cell's minimum level ranging between 0 mM 8 mM. Tolerant cells distinct gene expression profile non-tolerant cells. This form terms threshold (the concentration where growth ceases), yet outcome (at concentration, either grow normally or die, no phenotype), not associated any detectable genetic mutations. Moreover, population dynamic, changing over time response conditions. characterized this phenomenon using bulk liquid culture experiments, colony tracking, flow cytometry, single-cell time-lapse microscopy, transcriptomics, genome resequencing. Finally, used mathematical modeling better understand processes by phenotype, evidence for both stochastic, bidirectional diversification responsive, directed shifts, depending substrate presence toxin.

Язык: Английский

Diversity of bet‐hedging strategies in microbial communities—Recent cases and insights DOI
Luiza P. Morawska, Jhonatan A. Hernandez‐Valdes, Oscar P. Kuipers

и другие.

WIREs Mechanisms of Disease, Год журнала: 2021, Номер 14(2)

Опубликована: Ноя. 1, 2021

Abstract Microbial communities are continuously exposed to unpredictable changes in their environment. To thrive such dynamic habitats, microorganisms have developed the ability readily switch phenotypes, resulting a number of differently adapted subpopulations expressing various traits. In evolutionary biology, particular case phenotypic heterogeneity that evolved an unpredictably changing environment has been defined as bet‐hedging. Bet‐hedging is risk‐spreading strategy where isogenic populations stochastically (randomly) diversify often maladapted individuals suffer lower reproductive success. This fitness trade‐off specific may selective advantage upon sudden environmental shift. Thus, bet‐hedging allows persist very but with cost. recent years, numerous examples different observed, some suggesting Here, we highlight latest reports concerning phenomena show how versatile this within microbial realms. article categorized under: Infectious Diseases > Molecular and Cellular Physiology

Язык: Английский

Процитировано

51
Trade‐offs between the instantaneous growth rate and long‐term fitness: Consequences for microbial physiology and predictive computational models DOI Creative Commons
Frank J. Bruggeman, Bas Teusink, Ralf Steuer

и другие.

BioEssays, Год журнала: 2023, Номер 45(10)

Опубликована: Авг. 9, 2023

Abstract Microbial systems biology has made enormous advances in relating microbial physiology to the underlying biochemistry and molecular biology. By meticulously studying model microorganisms, particular Escherichia coli Saccharomyces cerevisiae , increasingly comprehensive computational models predict metabolic fluxes, protein expression, growth. The modeling rationale is that cells are constrained by a limited pool of resources they allocate optimally maximize fitness. As consequence, expression proteins at expense others, causing trade‐offs between cellular objectives such as instantaneous growth, stress tolerance, capacity adapt new environments. While current remarkably predictive for E. S. when grown laboratory environments, this may not hold other growth conditions microorganisms. In contribution, we therefore discuss relationship rate, resources, long‐term We uses limitations models, rapidly changing adverse propose classify strategies based on Grimes's CSR framework.

Язык: Английский

Процитировано

19
Case Studies in the Assessment of Microbial Fitness: Seemingly Subtle Changes Can Have Major Effects on Phenotypic Outcomes DOI Creative Commons
Sarah B. Worthan,

Robert D. P. McCarthy,

Megan G. Behringer

и другие.

Journal of Molecular Evolution, Год журнала: 2023, Номер 91(3), С. 311 - 324

Опубликована: Фев. 8, 2023

Abstract Following the completion of an adaptive evolution experiment, fitness evaluations are routinely conducted to assess magnitude adaptation. In doing so, proper consideration should be given when determining appropriate methods as trade-offs may exist between accuracy and throughput. Here, we present three instances in which small changes framework or execution significantly impacted outcomes. The first case illustrates that discrepancies conclusions can arise depending on approach evaluating fitness, culture vessel used, sampling method. second reveals variations environmental conditions occur associated with material. Specifically, these subtle greatly affect microbial physiology leading pH distorting measurements. Finally, last reports heterogeneity CFU formation time result inaccurate conclusions. Based each case, considerations recommendations presented for future experiments.

Язык: Английский

Процитировано

18
Second-Generation Digital Health Platforms: Placing the Patient at the Center and Focusing on Clinical Outcomes DOI Creative Commons
Yaron Ilan

Frontiers in Digital Health, Год журнала: 2020, Номер 2

Опубликована: Дек. 3, 2020

Artificial intelligence (AI) digital health systems have drawn much attention over the last decade. However, their implementation into medical practice occurs at a slower pace than expected. This paper reviews some of achievements first-generation AI systems, and barriers facing practice. The development second-generation is discussed with focus on overcoming these obstacles. Second-generation are aimed focusing single subject improving patients' clinical outcomes. A personalized closed-loop system designed to improve end-organ function patient's response chronic therapies presented. introduces platform which implements therapeutic regimen quantifiable individualized-variability patterns its algorithm. achieve clinically meaningful endpoint by ensuring that will sustainable effect while compensatory mechanisms associated disease progression drug resistance. expected assist patients providers in adopting implementing everyday care.

Язык: Английский

Процитировано

46
Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer DOI Creative Commons
Sarthak Sahoo,

Soundharya Ramu,

Madhumathy G Nair

и другие.

iScience, Год журнала: 2024, Номер 27(7), С. 110116 - 110116

Опубликована: Май 27, 2024

Highlights•Luminal signature is closely associated with epithelial in breast cancer•Basal correlates well a hybrid epithelial-mesenchymal signature•Basal cancer exhibits higher heterogeneity patterns•Mathematical modeling of underlying gene networks explains observed heterogeneitySummaryIntra-tumoral phenotypic promotes tumor relapse and therapeutic resistance remains an unsolved clinical challenge. Decoding the interconnections among different biological axes plasticity crucial to understand molecular origins heterogeneity. Here, we use multi-modal transcriptomic data—bulk, single-cell, spatial transcriptomics—from cell lines primary samples, identify associations between transition (EMT) luminal-basal plasticity—two key processes that enable We show luminal strongly associates state, but basal epithelial/mesenchymal phenotype(s) Mathematical core regulatory representative crosstalk elucidate mechanistic underpinnings from data. Our systems-based approach integrating data analysis mechanism-based offers predictive framework characterize intra-tumor interventions restrict it.Graphical abstract

Язык: Английский

Процитировано

6
On the networked architecture of genotype spaces and its critical effects on molecular evolution DOI Creative Commons
Jacobo Aguirre, Pablo Catalán, José A. Cuesta

и другие.

Open Biology, Год журнала: 2018, Номер 8(7)

Опубликована: Июль 1, 2018

Evolutionary dynamics is often viewed as a subtle process of change accumulation that causes divergence among organisms and their genomes. However, this interpretation an inheritance gradualistic view has been challenged at the macroevolutionary, ecological molecular level. Actually, when complex architecture genotype spaces taken into account, evolutionary populations becomes intrinsically non-uniform, sharing deep qualitative quantitative similarities with slowly driven physical systems: nonlinear responses analogous to critical transitions, sudden state changes or hysteresis, others. Furthermore, phenotypic plasticity inherent genotypes transforms classical fitness landscapes multiscapes where adaptation in response environmental may be very fast. The nature adaptive processes deeply dependent on network-of-networks multilayered structure map from function we begin unveil.

Язык: Английский

Процитировано

33
Aggregation of Nontuberculous Mycobacteria Is Regulated by Carbon-Nitrogen Balance DOI Creative Commons
William H. DePas, Megan Bergkessel, Dianne K. Newman

и другие.

mBio, Год журнала: 2019, Номер 10(4)

Опубликована: Авг. 12, 2019

Free-living bacteria can assemble into multicellular structures called biofilms. Biofilms help tolerate multiple stresses, including antibiotics and the host immune system. Nontuberculous mycobacteria are a group of emerging opportunistic pathogens that utilize biofilms to adhere household plumbing showerheads avoid phagocytosis by cells. Typically, regulate biofilm formation controlling expression adhesive attach surfaces other bacterial Mycobacteria harbor unique cell wall built chiefly long-chain mycolic acids confers hydrophobicity has been thought cause constitutive aggregation in liquid media. Here we show is instead regulated process dictated balance available carbon nitrogen. Understanding metabolic cues transition between planktonic aggregated cells reveals an inroad through targeted therapeutics.

Язык: Английский

Процитировано

32
Single-Cell Infrared Microspectroscopy Quantifies Dynamic Heterogeneity of Mesenchymal Stem Cells during Adipogenic Differentiation DOI Open Access
Yadi Wang, Wentao Dai,

Zhixiao Liu

и другие.

Analytical Chemistry, Год журнала: 2020, Номер 93(2), С. 671 - 676

Опубликована: Дек. 8, 2020

The central relevance of cellular heterogeneity to biological phenomena raises the rational needs for analytical techniques with single-cell resolution. Here, we developed a FTIR microspectroscopy-based method quantitative evaluation by calculating cell-to-cell similarity distance infrared spectral data. Based on this method, revealed phenotypes might reflect dynamic changes in cell population during adipogenic differentiation human mesenchymal stem cells. These findings provide an alternative label-free optical approach quantifying heterogeneity, and combination other analysis tools will be very helpful understanding genotype-to-phenotype relationship populations.

Язык: Английский

Процитировано

25
Reducing phenotypic instabilities of a microbial population during continuous cultivation based on cell switching dynamics DOI
Thai Minh Nguyen,

Samuel Telek,

Andrew Zicler

и другие.

Biotechnology and Bioengineering, Год журнала: 2021, Номер 118(10), С. 3847 - 3859

Опубликована: Июнь 15, 2021

Predicting the fate of individual cells among a microbial population (i.e., growth and gene expression) remains challenge, especially when this is exposed to very dynamic environmental conditions, such as those encountered during continuous cultivation. Indeed, nature cultivation process implies potential diversification resulting in genotypic phenotypic heterogeneity. The present work focused on induction arabinose operon Escherichia coli model system study cultivations. As preliminary step, green fluorescent protein (GFP) level triggered by an arabinose-inducible ParaBAD promoter was tracked flow cytometry chemostat cultivations with glucose-arabinose co-feeding. For wide range co-feeding concentrations chemostats, simultaneous occurrence GFP positive negative subpopulation observed. In second set experiments, performed adding glucose continuously based capability switch from low high expression states, technology setup called segregostat. segregostat mode, on-line analysis used for adjusting arabinose/glucose transitions switching profiles population. This strategy allowed finding appropriate pulsing frequency, leading prolonged maintenance limited increase diversity more than 60 generations. results suggest that steady forcing into given trajectory may not be best controlling cell populations. Instead, allowing periodically around predefined threshold seems robust oscillations, but within predictable behavior range.

Язык: Английский

Процитировано

21
Bacteriophage Treatment Induces Phenotype Switching and Alters Antibiotic Resistance of ESBL Escherichia coli DOI Creative Commons

Árpád Rózsa,

László Orosz, Nikoletta Szemerédi

и другие.

Antibiotics, Год журнала: 2025, Номер 14(1), С. 76 - 76

Опубликована: Янв. 13, 2025

Background/Objectives: Bacteriophage therapy represents a promising strategy to combat multidrug-resistant pathogens, such as Escherichia coli. In this study, we explored the effects of bacteriophage infection on an Extended Spectrum Beta-Lactamase (ESBL) positive E. coli isolate. Methods: We used next generation sequencing, proteomics and phenotypic screens investigate effect infections metabolism resistance phenotypes. Results: The led notable alterations in colony morphology, indicating profound changes bacterial metabolism. Proteomic analysis revealed significant shifts protein expression, with 65 proteins upregulated 246 downregulated post-infection. were involved various metabolic pathways, including nucleic acid, lipid metabolism, iron acquisition. treatment also increased membrane permeability. Altogether, these permeability may lead general reduction antibiotic resistance. Indeed, bacteriophage-infected exhibited sensitivity classes antibiotics, beta-lactams, fluoroquinolones, trimethoprim-sulfamethoxazole, aminoglycosides. Conclusions: Our findings highlight potential adjunct existing enhancing their efficacy against resistant strains.

Язык: Английский

Процитировано

0