GMP-Cor: Quantifying Transcriptional Dysregulation in Antibiotic Tolerance and Persistence

Authors

Gutfreund, A., Rotem, A., Ronin, I., Rosenthal, A. Z., Agam, O., Balaban, N. Q.

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.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Nov 2026.

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