Antibiotics and Aggresomes: How Bacteria Bounce Back

Aggresomes within bacteria cells help these cells overcome antibiotics. Scientists uncover how they work and propose how to counteract them.

By Tanvi Patil

You’ve probably heard of bacteria developing resistance to antibiotics. This mechanism allows pesky microbes to survive even the most drug-bombarded conditions. But what exactly makes them so efficient at bouncing back? Scientists believe the answer to this question lies in aggresomes, which are small conglomerates of protein and RNA that allow bacteria to resume replication after stress exposure of antibiotics. 

The history of treating bacterial infections

From serious epidemics such as the Black Death of the 1300s and waves of cholera that claimed millions of lives in the 1800s to the lighter food poisoning instances we have all dealt with, bacteria have proven their existence by causing health outbreaks since the dawn of time. 

Prior to the discovery of modern antibiotics, medical professionals and ancient civilizations had crafted their own systems to mitigate bacterial infection. For instance, the Nubian civilization consumed grain-derived beer found to be rich in tetracycline, a molecule that was later discovered to be an antibiotic against several bacterial infections. Similarly, bloodletting, a procedure where blood was physically removed from the body using needles, was largely practiced in Europe and colonized settlements as it followed ancient medical notions of excessive blood causing illness. Furthermore, harsh naturally occurring elements and compounds such as mercury and bromine were often topically or subcutaneously administered for treating wound infections, but we now know what the longevity and standard of living for these patients looks like. 

Overall, while these treatments existed for treating bacterial infections, antibiotics proved to be far more effective upon their discovery in the 1900s, leading to the dissolution of these traditional practices. Antibiotics are broadly defined as molecules produced by one bacterial species that can kill another. For example, penicillin—produced by Penicillium notatum—inhibits the growth of several bacteria including Staphylococcus. Over time, hundreds of antibiotics have been discovered, and treatment often incorporates a mixture of these. 

Learn more about antibiotics and bacteria: Searching for Alternatives to Antibiotics

The silent killer: antibiotic resistance

Though antibiotic discovery and treatment was initially promising, it has since revealed the greatest killer: antibiotic resistance. All life on earth is prone to changes in their genetic code due to physical factors such as radiation and spontaneous events when the DNA is copied for cell division. Mutations that prove to be beneficial are incorporated into the greater population over time, while the disadvantages fizzle out. However, due to the fast replicating nature of bacteria, they are prone to more rapid selection of mutations that allow them to persist through drug-based treatments, creating resistance. Bacteria that become resistant to several drugs are referred to as multi-drug resistant (MDR). MDR bacteria have great potential to become superbugs that are extremely difficult to control and eradicate. This drawback has led to researching how bacteria become resistant, and using it to engineer new classes of therapies against bacterial infections. 

RELATED: A New Way to Treat Antibiotic Resistant Bacteria

Aggresomes: What are they and why do they work?

One possible target for mitigating bacterial infections are therapies attacking aggresomes. Aggresomes are small clusters of protein and RNA found within bacteria. They protect key bacterial DNA and RNA, allowing them to quickly bounce back after antibiotic-induced stress. Scientists teamed up from Wuhan University, York University (UK), and Peking University to research and publish their findings on aggresomes. They characterized the mRNA (RNA ready to be turned into a protein through a process called translation) contained within these aggresomes typically encoded for proteins involved in growth processes. Thus, the machinery needed for a bacteria cell to rebound is easily accessible when the aggresome dissolves in the absence of stress. The researchers also observed that bacteria with aggresomes yield more persistor cells (cells that are dormant) when the stressor is lifted. These cells are special because they can switch back into an active and replicating state when antibiotics are removed from the system.

But how exactly do these little clusters of protein and RNA actually protect themselves? Aggresomes are special because they are electrostatically exclusive, meaning they can prevent molecules of certain charges from getting in. Aggresomes, specifically, are negatively charged due to the accumulation of negatively charged RNA. One of the key degraders of RNA, ribonucleases, is also negatively charged. Similar to a magnet where opposite poles repulse each other, opposite charges also push each other away! This prevents ribonucleases from getting inside the aggresomes and cutting the RNA up, leaving it intact and ready to make proteins once the stress has been alleviated. 

The future of treating bacterial infections 

Aggresomes pose an interesting new avenue and target for therapies against infectious diseases. We may see therapies in the future that aim to dissolve the aggresome alongside antibiotics to decrease the frequency of resistance. Alternatively, the researchers of this study also propose the idea of developing positively charged ribonucleases to bypass the electrostatic selection aggresomes pose. 

Overall, this study uncovers an important aspect in understanding bacterial rebound after stress. It will be interesting to see how other discoveries in resistance can be coupled to develop more effective therapies against bacterial infections. 

In the meantime, we can take a step in mitigating antibiotic resistance by properly washing our hands with soap and warm water for 20 seconds to decrease the risk of bacterial infections.

This study was published in the peer-reviewed journal Nature Microbiology. 

References

Bollen, C., Dewachter, L., & Michiels, J. (2021). Protein Aggregation as a Bacterial Strategy to Survive Antibiotic Treatment. Frontiers in Molecular Biosciences, 8, 669664. https://doi.org/10.3389/fmolb.2021.669664 

Pei, L., Xian, Y., Yan, X., Schaefer, C., Syeda, A. H., Howard, J. A. L., Zhang, W., Liao, H., Bai, F., Leake, M. C., & Pu, Y. (2025). Aggresomes protect mRNA under stress in Escherichia coli. Nature Microbiology, 10, 2323–2337. doi: 10.1038/s41564-025-02086-5

Featured image: A variety of different bacteria – testing for antimicrobial resistance. UK Department for International Development. Credit: DFID/ Will Crowne. Licensed under CC BY 2.0.