SOS-independent prophage induction pathways and their contributions to antibiotic resistance gene dissemination: advances and controversies
6 affiliations
- 1North Henan Medical University
- 2Chinese Society of Biotechnology
- 3Zhejiang Chinese Medical University
- 4Zhengzhou Central Hospital
- 5Henan Medical University
- 6Jilin University
Abstract
Temperate bacteriophages integrate into bacterial chromosomes as prophages, which are widespread across sequenced bacterial genomes and serve as key mobile genetic elements mediating horizontal gene transfer and the global dissemination of antibiotic resistance genes (ARGs). For decades, prophage induction has been thought to rely almost entirely on the canonical SOS DNA damage response triggered by DNA-damaging agents such as fluoroquinolones and mitomycin C; however, accumulating experimental evidence shows that multiple SOS-independent regulatory circuits also drive the lysogeny-to-lysis switch in response to non-DNA-damaging physiological and environmental cues. In this mini-review, we classify SOS-independent prophage induction pathways into five major categories: quorum sensing-mediated regulation, metabolic and oxidative stress-triggered activation, induction by sub-inhibitory concentrations of non-DNA-damaging antibiotics, spontaneous induction driven by stochastic gene expression noise, and modulation by physiological and environmental factors such as bile acids and osmotic stress. We summarize the molecular basis of each pathway and examine available empirical evidence linking these induction routes to phage-mediated ARG dissemination across clinical, intestinal, and environmental microbial ecosystems. We further outline four core unresolved debates in the field: the relative quantitative contribution of SOS-independent versus SOS-dependent induction to resistance spread, the mechanistic classification of sub-inhibitory antibiotic effects, the gap between bioinformatic predictions of prophage-associated ARGs and their functional transmissibility, and the limited taxonomic scope of current mechanistic research. We conclude by discussing implications for antimicrobial resistance stewardship and highlighting priority directions for future quantitative and functional investigations.
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BibTeX
@article{sima2026sosindependent,
title = {{SOS-independent prophage induction pathways and their contributions to antibiotic resistance gene dissemination: advances and controversies}},
author = {Jinwen Sima and Suling Li and Qingju Bian and Yuanjie Chen and Siyu Ji and Yusi Yan and Zewen Zhao and Anqi Liu and Xianxue Shi},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1972752},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1972752/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - SOS-independent prophage induction pathways and their contributions to antibiotic resistance gene dissemination: advances and controversies
AU - Jinwen Sima
AU - Suling Li
AU - Qingju Bian
AU - Yuanjie Chen
AU - Siyu Ji
AU - Yusi Yan
AU - Zewen Zhao
AU - Anqi Liu
AU - Xianxue Shi
PY - 2026
DA - 2026/10/22
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1972752
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1972752/full
AB - Temperate bacteriophages integrate into bacterial chromosomes as prophages, which are widespread across sequenced bacterial genomes and serve as key mobile genetic elements mediating horizontal gene transfer and the global dissemination of antibiotic resistance genes (ARGs). For decades, prophage induction has been thought to rely almost entirely on the canonical SOS DNA damage response triggered by DNA-damaging agents such as fluoroquinolones and mitomycin C; however, accumulating experimental evidence shows that multiple SOS-independent regulatory circuits also drive the lysogeny-to-lysis switch in response to non-DNA-damaging physiological and environmental cues. In this mini-review, we classify SOS-independent prophage induction pathways into five major categories: quorum sensing-mediated regulation, metabolic and oxidative stress-triggered activation, induction by sub-inhibitory concentrations of non-DNA-damaging antibiotics, spontaneous induction driven by stochastic gene expression noise, and modulation by physiological and environmental factors such as bile acids and osmotic stress. We summarize the molecular basis of each pathway and examine available empirical evidence linking these induction routes to phage-mediated ARG dissemination across clinical, intestinal, and environmental microbial ecosystems. We further outline four core unresolved debates in the field: the relative quantitative contribution of SOS-independent versus SOS-dependent induction to resistance spread, the mechanistic classification of sub-inhibitory antibiotic effects, the gap between bioinformatic predictions of prophage-associated ARGs and their functional transmissibility, and the limited taxonomic scope of current mechanistic research. We conclude by discussing implications for antimicrobial resistance stewardship and highlighting priority directions for future quantitative and functional investigations.
SN - 1664-302X
ER -