A groundbreaking study by researchers from Wuhan University, York University (UK), and Peking University has uncovered how Escherichia coli (E. coli) persister bacteria survive antibiotics by protecting their genetic instructions. The work, published in Nature Microbiology, offers new hope for tackling chronic, recurring infections.
Persister bacteria, which enter a dormant state to survive antibiotics that target active cells, are linked to over 20% of chronic infections and resist current treatments. Understanding their survival mechanisms could lead to new ways to combat recurring infections. This study utilized E. coli bacteria as a model and found that prolonged stress leads to the increased formation of aggresomes (membraneless droplets) and the enrichment of mRNA (molecules that carry instructions for making proteins) within them, which enhances the ability of E. coli to survive and recover from stress.
Key Findings
They used multiple approaches, including imaging, modelling, and transcriptomics, to show that prolonged stress leading to ATP(fuel for all living cells) depletion in Escherichia coli results in increased aggresome formation, their compaction, and enrichment of mRNA within aggresomes compared to the cytosol(the liquid inside of cells). Transcript length was longer in aggresomes compared to the cytosol. Mass spectrometry showed exclusion of mRNA ribonuclease(an enzyme that breaks down RNA) from aggresomes, which was due to negative charge repulsion. Experiments with fluorescent reporters and disruption of aggresome formation showed that mRNA storage within aggresomes promoted translation and was associated with reduced lag phases during growth after stress removal. These findings suggest that mRNA storage within aggresomes confers an advantage for bacterial survival and recovery from stress.
Future Implications
This breakthrough illuminates how persister cells survive and revive after antibiotic treatment. By targeting aggresomes, new drugs could disrupt this protective mechanism, preventing bacteria from storing mRNA and making them more vulnerable to elimination, thus reducing the risk of infection relapse.
*This article is featured in PKU News "Why It Matters" series. More from this series.
