Rapid enhancement of antibiotic resistance and divergent remodeling of gene expression in single cells of bacteria
Abstract
Exposing bacterial cell populations to antibiotics often results in the emergence of descendants with enhanced resistance. Phenotypic heterogeneity and global physiological responses are thought to contribute to resistance evolution. However, identifying the specific stages of drug exposure where phenotypic heterogeneity and physiological responses play critical roles remains elusive. Using long-term single-cell lineage tracking of an Escherichia coli resistance model, here we reveal that resistance-enhanced cells emerge rapidly within a few generations in a clonal bacterial cell population under chloramphenicol (Cp) exposure and stably transmit the enhanced resistance for hundreds of generations in the presence of Cp. High expression of a resistance protein was advantageous during the initial period of drug exposure, but conferred only a marginal fitness advantage during the period of resistance enhancement. Transcriptomic profiles of resistance-enhanced cell populations were lineage-specific, suggesting that multiple gene expression states can support enhanced resistance. Altogether, these results suggest that an interplay between initial phenotypic heterogeneity and divergent remodeling of gene expression drives the rapid acquisition of enhanced antibiotic resistance.
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BibTeX
@misc{umetani2026rapid,
title = {{Rapid enhancement of antibiotic resistance and divergent remodeling of gene expression in single cells of bacteria}},
author = {Miki Umetani and Mikihiro Hashimoto and Sayo Akiyoshi and Reiko Okura and Natsue Sakata and Hazuki Kotani and Edo Kussell and Chikara Furusawa and Yuichi Wakamoto},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.22.760911},
url = {https://www.biorxiv.org/content/10.64898/2026.10.22.760911v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Rapid enhancement of antibiotic resistance and divergent remodeling of gene expression in single cells of bacteria
AU - Miki Umetani
AU - Mikihiro Hashimoto
AU - Sayo Akiyoshi
AU - Reiko Okura
AU - Natsue Sakata
AU - Hazuki Kotani
AU - Edo Kussell
AU - Chikara Furusawa
AU - Yuichi Wakamoto
PY - 2026
DA - 2026/10/22
PB - bioRxiv
DO - 10.64898/2026.10.22.760911
UR - https://www.biorxiv.org/content/10.64898/2026.10.22.760911v1
AB - Exposing bacterial cell populations to antibiotics often results in the emergence of descendants with enhanced resistance. Phenotypic heterogeneity and global physiological responses are thought to contribute to resistance evolution. However, identifying the specific stages of drug exposure where phenotypic heterogeneity and physiological responses play critical roles remains elusive. Using long-term single-cell lineage tracking of an Escherichia coli resistance model, here we reveal that resistance-enhanced cells emerge rapidly within a few generations in a clonal bacterial cell population under chloramphenicol (Cp) exposure and stably transmit the enhanced resistance for hundreds of generations in the presence of Cp. High expression of a resistance protein was advantageous during the initial period of drug exposure, but conferred only a marginal fitness advantage during the period of resistance enhancement. Transcriptomic profiles of resistance-enhanced cell populations were lineage-specific, suggesting that multiple gene expression states can support enhanced resistance. Altogether, these results suggest that an interplay between initial phenotypic heterogeneity and divergent remodeling of gene expression drives the rapid acquisition of enhanced antibiotic resistance.
SN - 2692-8205
ER -