The Role of Integration Host Factor in Escherichia coli Persister Formation DOI

Samantha Nicolau,

Kim Lewis

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 4, 2022

Persisters represent a small subpopulation of cells that are tolerant killing by antibiotics and implicated in the recalcitrance chronic infections to antibiotic therapy. One general theme has emerged regarding persisters formed different bacterial species, namely, state relative dormancy characterized diminished activity targets. Within this framework, number studies have linked persister formation stochastic decreases energy-generating components, leading low ATP target activity. In study, we screen knockouts main global regulators Escherichia coli for their effect on persisters. A knockout integration host factor (IHF) had elevated level This was accompanied an overexpression isocitrate dehydrogenase (Icd) downregulation lyase (AceA), two genes located at bifurcation between tricarboxylic acid (TCA) cycle glyoxylate bypass. Using translational ihfA-mVenus fusion, sort out rare bright cells, is enriched Our results suggest noise expression ihf produces with Icd/high AceA, diverting substrates into bypass, which ATP, antibiotic-tolerant We further examine simple model, lac operon, show lacI repressor increases operon formation. quenching serves as approach determine nature variety species conditions. IMPORTANCE phenotypic variants survive exposure through temporary dormancy. Mutants increased levels been identified clinical isolates, evidence suggests these contribute treatment failure. Understanding underlying mechanism tolerance important developing therapeutic approaches treat infections. regulator, IHF, plays role find IHF contributes formation, likely regulating switch TCA efficiently energy extend study model when grown lactose sole carbon source, its influences determines quenched providing test involvement gene

Language: Английский

Ecology and evolution of antibiotic persistence DOI
Laure Verstraete, Bram Van den Bergh, Natalie Verstraeten

et al.

Trends in Microbiology, Journal Year: 2021, Volume and Issue: 30(5), P. 466 - 479

Published: Nov. 6, 2021

Language: Английский

Citations

53
Modulating the evolutionary trajectory of tolerance using antibiotics with different metabolic dependencies DOI Creative Commons

Erica J. Zheng,

Ian W. Andrews,

Alexandra Grote

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 9, 2022

Antibiotic tolerance, or the ability of bacteria to survive antibiotic treatment in absence genetic resistance, has been linked chronic and recurrent infections. Tolerant cells are often characterized by a low metabolic state, against which most clinically used antibiotics ineffective. Here, we show that tolerance readily evolves strongly dependent on bacterial metabolism, but does not arise whose efficacy is only minimally affected state. We identify mechanism evolution E. coli involving deletion sodium-proton antiporter gene nhaA, results downregulated metabolism upregulated stress responses. Additionally, find cycling with different dependencies interrupts vitro, increasing lifetime efficacy. Our work highlights potential for limiting occurrence extent accounting metabolism.

Language: Английский

Citations

39
Advances in linking single-cell bacterial stress response to population-level survival DOI Creative Commons
Razan N. Alnahhas, Mary J. Dunlop

Current Opinion in Biotechnology, Journal Year: 2023, Volume and Issue: 79, P. 102885 - 102885

Published: Jan. 13, 2023

Language: Английский

Citations

22
Probing transient memory of cellular states using single-cell lineages DOI Creative Commons
Abhyudai Singh,

Michael Saint-Antoine

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 7, 2023

The inherent stochasticity in the gene product levels can drive single cells within an isoclonal population to different phenotypic states. dynamic nature of this intercellular variation, where individual transition between states over time, makes it a particularly hard phenomenon characterize. We reviewed recent progress leveraging classical Luria-Delbrück experiment infer transient heritability cellular Similar original experiment, were first grown into cell colonies, and then, fraction residing was assayed for each colony. discuss modeling approaches capturing state transitions growing highlight formulas that identify kinetics switching from extent colony-to-colony fluctuations. utility method identifying multi-generational memory both expression is illustrated across diverse biological systems cancer drug resistance, reactivation human viruses, immune responses. In summary, fluctuation-based methodology provides powerful approach elucidating cell-state

Language: Английский

Citations

20
New Strategies to Kill Metabolically-Dormant Cells Directly Bypassing the Need for Active Cellular Processes DOI Creative Commons
Karolina Stojowska‐Swędrzyńska, Dorota Kuczyńska‐Wiśnik, Ewa Laskowska

et al.

Antibiotics, Journal Year: 2023, Volume and Issue: 12(6), P. 1044 - 1044

Published: June 12, 2023

Antibiotic therapy failure is often caused by the presence of persister cells, which are metabolically-dormant bacteria capable surviving exposure to antimicrobials. Under favorable conditions, persisters can resume growth leading recurrent infections. Moreover, several studies have indicated that may promote evolution antimicrobial resistance and facilitate selection specific resistant mutants; therefore, in light increasing numbers multidrug-resistant infections worldwide, developing efficient strategies against dormant cells paramount importance. In this review, we present discuss efficacy various agents whose activity independent metabolic status as they target cell envelope structures. Since biofilm-environment for formation subpopulations, anti-persister should also include destroy biofilm matrix or inhibit development. This article reviews examples selected wall hydrolases, polysaccharide depolymerases peptides. Their combination with standard antibiotics seems be most promising approach combating persistent

Language: Английский

Citations

15
Intracellular persister: A stealth agent recalcitrant to antibiotics DOI Creative Commons
Nicolas Personnic, Patricia Doublet, Sophie Jarraud

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: March 31, 2023

The bulk of bacteria transiently evading appropriate antibiotic regimes and recovered from non-resolutive infections are commonly refer to as persisters. In this mini-review, we discuss how persisters stem the interplay between pathogen cellular defenses mechanisms its underlying heterogeneity.

Language: Английский

Citations

14
Drug tolerance and persistence in bacteria, fungi and cancer cells: Role of non-genetic heterogeneity DOI Creative Commons
Imane El Meouche, Paras Jain, Mohit Kumar Jolly

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 49, P. 102069 - 102069

Published: Aug. 8, 2024

Language: Английский

Citations

6
Single-Cell Technologies to Study Phenotypic Heterogeneity and Bacterial Persisters DOI Creative Commons
Patricia J. Hare, Travis J. LaGree, Brandon A. Byrd

et al.

Microorganisms, Journal Year: 2021, Volume and Issue: 9(11), P. 2277 - 2277

Published: Nov. 1, 2021

Antibiotic persistence is a phenomenon in which rare cells of clonal bacterial population can survive antibiotic doses that kill their kin, even though the entire genetically susceptible. With treatment failure on rise, there growing interest understanding molecular mechanisms underlying phenotypic heterogeneity and persistence. However, elucidating these cell states be technically challenging. The advent single-cell techniques has enabled us to observe quantitatively investigate individual complex, phenotypically heterogeneous populations. In this review, we will discuss current technologies for studying persister phenotypes, including fluorescent tags biosensors used elucidate cellular processes; advances flow cytometry, mass spectrometry, Raman spectroscopy, microfluidics contribute high-throughput high-content information; next-generation sequencing powerful insights into genetic transcriptomic programs. We further existing knowledge gaps, cutting-edge address them, how microbiology potentially improve infectious disease outcomes.

Language: Английский

Citations

30
Transcription-coupled DNA repair underlies variation in persister awakening and the emergence of resistance DOI
Dorien Wilmaerts, Focant Charline, Paul Matthay

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(9), P. 110427 - 110427

Published: March 1, 2022

Language: Английский

Citations

23
Microfluidics for long-term single-cell time-lapse microscopy: Advances and applications DOI Creative Commons
Paige Allard, Fotini Papazotos, Laurent Potvin-Trottier

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 12, 2022

Cells are inherently dynamic, whether they responding to environmental conditions or simply at equilibrium, with biomolecules constantly being made and destroyed. Due their small volumes, the chemical reactions inside cells stochastic, such that genetically identical display heterogeneous behaviors gene expression profiles. Studying these dynamic processes is challenging, but development of microfluidic methods enabling tracking individual prokaryotic microscopy over long time periods under controlled growth has led many discoveries. This review focuses on recent developments one device nicknamed mother machine. We overview original design, experimental setup, challenges associated this platform. then describe for analyzing experiments using automated image segmentation tracking. further discuss modifications setup allow time-varying control, replicating batch culture conditions, cell screening based behaviors, accommodate a variety microbial species. Finally, highlights discoveries enabled by technology in diverse fields, as cell-size genetic mutations, cellular aging, synthetic biology.

Language: Английский

Citations

23