Priestia megaterium cells are primed for surviving lethal doses of antibiotics and chemical stress

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Фев. 8, 2025

Antibiotic resistant infections kill millions worldwide yearly. However, a key factor in recurrent is antibiotic persisters. Persisters are not inherently antibiotic-resistant but can withstand exposure by entering non-dividing state. This tolerance often results prolonged usage, increasing the likelihood of developing strains. Here, we show existence "primed cells" Gram-positive bacterium Priestia megaterium, formerly known as Bacillus megaterium. These cells pre-adapted to become persisters prior lethal stress. Remarkably, this prepared state passed down through multiple generations via epigenetic memory, enhancing survival against antibiotics and other chemical Previously, two distinct types were proposed: Type I II, formed during stationary log phases, respectively. our findings reveal that primed contribute an increase transition with no evidence supporting phenotypes between II

Язык: Английский

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Induced tolerance to UV stress drives survival heterogeneity in isogenicE. colicell populations

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

The emergence of transiently tolerant bacterial subpopulations challenges our understanding stress tolerance mechanisms. While much is known about antibiotic tolerance, it remains unclear whether similar mechanisms contribute to survival under ultraviolet (UV) stress. Here, we employed a modified Luria-Delbrück fluctuation test investigate the presence pre-existing UV-tolerant in Escherichia coli . Our results showed no significant evidence pre-stress UV tolerance. Instead, data suggest that primarily driven by inducible DNA repair responses activated after exposure. Furthermore, sequential low-dose exposures yielded higher-than-expected survival, suggesting transient can be induced following initial exposure, likely through active processes. These findings indicate E. survives via an induced, rather than pre-existing, mechanism

Язык: Английский

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Bursty Gene Expression in Single Cells and Expanding Populations: A Discrete Approach

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 25, 2025

Abstract Bursty protein production is a key source of gene expression noise. In this study, we analyze Markovian model cellular dynamics, where proteins are produced in geometrically distributed bursts. Extending model, incorporate feedback mechanism by assuming that higher levels reduce both cell growth and decay rates. We study single-cell dynamics an expanding population. Without feedback, the level follows negative binomial distribution with same parameters cases. With however, population-level distributions differ, each expressible as mixture two framework-dependent parameters. Using numerical integration master population balance equations, calculate time-dependent settings. This work extends previous continuous models provides new insights into how expansion influences intrinsic heterogeneity.

Язык: Английский

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Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 29, 2024

Abstract Random fluctuations (noise) in gene expression can be studied from two complementary perspectives: following a single cell over time or comparing between cells proliferating population at given time. Here, we systematically investigated scenarios where both perspectives lead to different levels of noise product. We first consider stable protein, whose concentration is diluted by cellular growth, and the protein inhibits growth high concentrations, establishing positive feedback loop. For stochastic model with molecular bursting products, analytically predict contrast steady-state distributions frameworks. Although amplifies expression, this amplification much higher framework compared also study other processes that even absence such dilution-based feedback. When considering randomness partitioning molecules daughters during mitosis, find single-cell perspective, independent cycle duration. In contrast, amplified perspective increasing cell-cycle Overall, our results show commonly used does not account for can, some cases, underestimate product levels. These have important implications studying inter-cellular variation stress-related programs across types are known inhibit growth.

Язык: Английский

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Optimisation of gene expression noise for cellular persistence against lethal events

Journal of Theoretical Biology, Год журнала: 2024, Номер unknown, С. 111996 - 111996

Опубликована: Ноя. 1, 2024

Язык: Английский

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