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Researchers from York University (UK), Peking University, and Wuhan University have discovered how Escherichia coli (E. coli) persister bacteria withstand drugs by safeguarding their genetic instructions.
The study, which was published in Nature Microbiology, gives new optimism for treating persistent infections.
Over 20% of chronic infections are caused by persister bacteria, which withstand existing treatments by becoming dormant in order to evade drugs that target active cells.
New strategies to fight recurrent infections may result from an understanding of the microbe’s survival processes. Using E. coli bacteria as a model, this research discovered that extended stress increases the production of aggresomes and enriches mRNA (molecules that contain instructions for building proteins), both of which improve E. coli’s capacity to withstand and recover from stress.
Using a variety of techniques, such as imaging, modeling, and transcriptomics, they demonstrated how long-term stress that causes ATP (the energy source for all living cells) to be depleted in Escherichia coli leads to an increase in the development of aggresomes, their compaction, and the enrichment of mRNA within aggresomes as opposed to the cytosol (fluid inside the cell).
Aggregesomes have longer mRNA transcripts than the cytosol. Due to negative charge repulsion, mass spectrometry revealed that mRNA ribonuclease, an enzyme that degrades RNA, was excluded from aggresomes.
mRNA storage inside aggresomes facilitated translation and was linked to fewer lag periods during growth after stress removal. These results imply that bacterial survival and stress recovery are enhanced by mRNA storage inside aggresomes.
This discovery sheds light on persister cells’ ability to endure and recover after antibiotic therapy. Novel medications that target aggresomes may interfere with this defense mechanism, preventing bacteria from accumulating mRNA and increasing their susceptibility to elimination, hence lowering the chance of infection recurrence.
Sources:
Linsen Pei et al. (2025). Aggresomes protect mRNA under stress in Escherichia coli, Nature Microbiology. DOI: 10.1038/s41564-025-02086-5
Unlocking how bacteria bounce back after antibiotics. https://phys.org/news/2025-09-bacteria-antibiotics.html
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