GMP-Cor: Quantifying Transcriptional Dysregulation in Antibiotic Tolerance and Persistence
- 1Hebrew University
Abstract
When cells are exposed to stress, they typically activate stress-response pathways and enter a regulated growth-arrest. But what if the stress overwhelms these pathways? In such cases, cells may enter a disrupted growth-arrest - a poorly adapted, abrupt cessation of growth, characterized by a broad distribution of lag times upon stress removal. This distribution underlies antibiotic persistence during stress recovery. Therefore, gaining a deeper understanding of the disrupted growth-arrest is important for developing more effective antibiotic therapies. In this study, we perform single cell RNA-seq on bacteria in disrupted conditions. We develop GMP-Cor: a metric to quantify dysregulation and analyze gene-gene correlation patterns in sparse single-cell data. We find that gene-gene correlations are significantly reduced in disrupted cells compared to regulated cells, providing direct evidence that this tolerance-enhanced state, along with its increased membrane sensitivity, is associated with global-dysregulation. We demonstrate that GMP-Cor can extend to other biological systems, such as persistent cancer cells, where it separates proliferating from drug-arrested cells.
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BibTeX
@misc{gutfreund2026gmpcor,
title = {{GMP-Cor: Quantifying Transcriptional Dysregulation in Antibiotic Tolerance and Persistence}},
author = {A. Gutfreund and A. Rotem and I. Ronin and A. Z. Rosenthal and O. Agam and N. Q. Balaban},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.763672},
url = {https://www.biorxiv.org/content/10.64898/2026.11.02.763672v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - GMP-Cor: Quantifying Transcriptional Dysregulation in Antibiotic Tolerance and Persistence
AU - A. Gutfreund
AU - A. Rotem
AU - I. Ronin
AU - A. Z. Rosenthal
AU - O. Agam
AU - N. Q. Balaban
PY - 2026
DA - 2026/11/02
PB - bioRxiv
DO - 10.64898/2026.11.02.763672
UR - https://www.biorxiv.org/content/10.64898/2026.11.02.763672v1
AB - When cells are exposed to stress, they typically activate stress-response pathways and enter a regulated growth-arrest. But what if the stress overwhelms these pathways? In such cases, cells may enter a disrupted growth-arrest - a poorly adapted, abrupt cessation of growth, characterized by a broad distribution of lag times upon stress removal. This distribution underlies antibiotic persistence during stress recovery. Therefore, gaining a deeper understanding of the disrupted growth-arrest is important for developing more effective antibiotic therapies. In this study, we perform single cell RNA-seq on bacteria in disrupted conditions. We develop GMP-Cor: a metric to quantify dysregulation and analyze gene-gene correlation patterns in sparse single-cell data. We find that gene-gene correlations are significantly reduced in disrupted cells compared to regulated cells, providing direct evidence that this tolerance-enhanced state, along with its increased membrane sensitivity, is associated with global-dysregulation. We demonstrate that GMP-Cor can extend to other biological systems, such as persistent cancer cells, where it separates proliferating from drug-arrested cells.
ER -