Development of adaptive anoikis resistance promotes metastasis that can be overcome by CDK8/19 Mediator kinase inhibition DOI Creative Commons
Mehri Monavarian, Emily Faith Page, Resha Rajkarnikar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 6, 2023

Anoikis resistance or evasion of cell death triggered by detachment into suspension is a hallmark cancer that concurrent with survival and metastasis. The effects frequent matrix encounters on the development anoikis in remains poorly defined. Here we show using panel ovarian models, repeated exposure to stress vitro followed attached recovery growth leads paralleling vivo ascites. This enhanced invasion, chemoresistance ability adapted cells metastasize distant sites. Adapted resistant heightened dependency oxidative phosphorylation can also evade immune surveillance. We find such acquired not genetic, as persists for finite duration absence stress. Transcriptional reprogramming however essential this process, acquisition adaptive exquisitely sensitive inhibition CDK8/19 Mediator kinase, pleiotropic regulator transcriptional reprogramming. Our data demonstrate after from direct contributor metastasis kinase during adaptation provides therapeutic opportunity prevent both local cancer.

Language: Английский

Prevalence and mechanisms of high-level carbapenem antibiotic tolerance in clinical isolates of Klebsiella pneumoniae DOI Creative Commons
Trevor Cross,

Facundo Torres,

Abigail P. McGee

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract Antibiotic tolerance is the ability of bacteria to survive normally lethal doses antibiotics for extended time periods. Clinically significant Enterobacterales, example, often exhibit high last-resort antibiotic meropenem. Meropenem associated with formation cell wall-deficient spheroplasts that readily recover rod shape and normal growth upon removal antibiotic. Both true prevalence tolerance, genetic mechanisms underlying it, remain poorly understood. Here, we find meropenem widespread among clinical Enterobacterales. Using forward genetics, uncover novel factors in a hypertolerant isolate ESKAPE pathogen Klebsiella pneumoniae . We multiple contribute envelope stress responses (PhoPQ, Cpx, Rcs OmpR/EnvZ) collectively promote spheroplast stability recovery, while lytic transglycosylase MltB counteracts it. Our data indicate isolates, outer membrane maintenance key factor promoting survival tolerant K.

Language: Английский

Citations

0
Induced tolerance to UV stress drives survival heterogeneity in isogenicE. colicell populations DOI Creative Commons
Shunsuke Ichikawa,

Midai Tanoue,

Junko S. Takeuchi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 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

Language: Английский

Citations

0
Fluctuation Test with Phenotypic Switching: A Unified Stochastic Approximation Framework DOI Creative Commons

Anna Hlubinová,

Pavol Bokes, Abhyudai Singh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 25, 2025

Abstract This paper examines a structurally symmetric fluctuation test experiment in which cell populations grow from single to set size before undergoing treatment. During growth, cells may acquire tolerance treatment through probabilistic events, are passed progeny. Motivated by recent research on drug microbial and cancer cells, the model also allows tolerant revert sensitive state, reflecting dynamic phenotypic switching. The master equation governing probability distribution of is solved via generating function method quasi-powers approximation. Depending parameters, be approximated stable (or its special case, normal distribution) or large deviations theory. In regime frequent switching, approach provides better agreement with numerical solutions, particularly at tails. Conversely, infrequent general distributions offer improved accuracy over Landau distribution, represents limiting case unidirectional

Language: Английский

Citations

0
Gram-positive bacteria are primed for surviving lethal doses of antibiotics and chemical stress DOI Creative Commons

Manisha Guha,

Abhyudai Singh, Nicholas C. Butzin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 29, 2024

Antibiotic resistance kills millions worldwide yearly. However, a major contributor to recurrent infections lies in small fraction of bacterial cells, known as persisters. These cells are not inherently antibiotic-resistant, yet they lead increased antibiotic usage, raising the risk developing resistant progenies. In population, individual exhibit considerable fluctuations their gene expression levels despite being cultivated under identical, stable conditions. This variability cell-to-cell characteristics (phenotypic diversity) within an isogenic population enables persister withstand exposure by entering non-dividing state. We recently showed existence "primed cells"

Language: Английский

Citations

2
Foodborne Viruses and Somatic Coliphages Occurrence in Fresh Produce at Retail from Northern Mexico DOI
Axel Ossio,

Fernanda Flores-Rodríguez,

Norma Heredia

et al.

Food and Environmental Virology, Journal Year: 2024, Volume and Issue: 16(1), P. 109 - 119

Published: Jan. 10, 2024

Language: Английский

Citations

1
Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives DOI
Zhanhao Zhang, Iryna Zabaikina, César Nieto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 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.

Language: Английский

Citations

1
Quantifying cancer cell plasticity with gene regulatory networks and single-cell dynamics DOI Creative Commons
Sarah M. Groves, Vito Quaranta

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 3

Published: Sept. 4, 2023

Phenotypic plasticity of cancer cells can lead to complex cell state dynamics during tumor progression and acquired resistance. Highly plastic stem-like states may be inherently drug-resistant. Moreover, in response therapy allow a evade treatment. In both scenarios, quantifying is essential for identifying high-plasticity or elucidating transition paths between states. Currently, methods quantify tend focus on 1) quantification quasi-potential based the underlying gene regulatory network system; 2) inference potency trajectory lineage tracing single-cell dynamics. Here, we explore these approaches associated computational tools. We then discuss implications each approach metrics, relevance treatment strategies.

Language: Английский

Citations

2
Sekwencjonowanie transkryptomu pojedynczych komórek: droga do odkrywania bioróżnorodności komórkowej DOI Open Access

Anna Samelak-Czajka,

Małgorzata Marszałek-Zeńczak, Paulina Jackowiak

et al.

Postępy Biochemii, Journal Year: 2024, Volume and Issue: 70(2), P. 190 - 203

Published: July 1, 2024

Single-cell transcriptomics (scRNA-Seq) is a breakthrough technology that has opened the way to characterizing gene expression with unprecedented resolution. It enabled discovery of cellular diversity organisms and tracing their developmental processes. A range technological solutions have been developed allow analysis tens thousands even million cells in single experiment, as well an extensive set tools for bioinformatics generated data. The wealth information provided by scRNA-Seq possibility using this method study cells, organoids, tissues entire determine its wide applications. In paper, we present experimental computational parts procedure, most important applications biomedicine, biology plant biology.

Language: Английский

Citations

0
Trehalose catalytic shift is an intrinsic factor in Mycobacterium tuberculosis that enhances phenotypic heterogeneity and multidrug resistance DOI
Hyungjin Eoh, Jae Jin Lee, Daniel Swanson

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Drug-resistance (DR) in many bacterial pathogens often arises from the repetitive formation of drug-tolerant bacilli, known as persisters. However, it is unclear whether

Language: Английский

Citations

0
Heritable non-genetic phenotypes are enriched for stress responses as a form of bet hedging DOI Creative Commons
Spencer Grissom,

Zachary Dixon,

Abhyudai Singh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract During manufacturing batches, Chinese hamster ovary (CHO) cells encounter critical levels of environmental stressors such as ammonia, lactate, and osmolality accumulation that can significantly reduce cell health productivity. It is therefore crucial stress adaptation resistance be factored into line development (CLD). In this study, we employee population-based transcriptomic differential gene expression analysis on stress-induced CHO to identify biomarkers displaying both heritable stress-responsive properties. Using workflow, 199 genes displayed transcriptional variability characteristic a bistable system formed four network communities co-fluctuating genes. These were enriched in related the regulation apoptotic processes expression/metabolic pathways. Seven identified promising for engineering stress-resistant phenotype. Genetic methods may employed future bias clonal populations higher tolerance stress, increasing productivity at-scale bioreactors.

Language: Английский

Citations

0