#FEMSmicroBlog: Toxin-antitoxin systems as survival tools for bacteria

22-07-2025

Bacteria require sophisticated sensing mechanisms to adjust their metabolisms to stressful conditions and hostile environments. One such mechanism is the toxin–antitoxin system, which plays crucial roles for bacteria to adapt to environmental challenges. The review “Insight into the environmental cues modulating the expression of bacterial toxin–antitoxin systems” in FEMS Microbiology Reviews highlights the diversity and complexity of environmental cues that influence the activation of toxin–antitoxin systems, as explained by Marie-Laure Pinel-Marie on this #FEMSmicroBlog. #FascinatingMicrobes

 

What are toxin-antitoxin systems?

When bacteria inhabit harsh environments, they rely on specialized mechanisms to survive. The toxin-antitoxin system consists of a pair of genes: one encodes a toxin that disrupts or halts essential cellular processes, while the other one encodes an antitoxin that neutralizes it.

Under normal conditions, the antitoxin keeps the toxin inactivated, assuring survival of the producing cell. However, under stress—such as nutrient deprivation, antibiotic exposure, or viral attack—the balance shifts. This activates the toxin, thereby slowing or stopping bacterial growth.

Toxin-antitoxin systems are widespread across bacterial species, though the number and types vary significantly. For instance, Mycobacterium tuberculosis harbors many toxin-antitoxin systems, while other bacteria may possess just a few or even none. There are currently eight recognized types of toxin-antitoxin systems, classified based on the nature of the antitoxin and the mechanism by which it inhibits the toxin.

The review “Insight into the environmental cues modulating the expression of bacterial toxin–antitoxin systems” in FEMS Microbiology Reviews provides an overview of three types of environmental cues that activate toxin-antitoxin systems.

The regulation of toxin–antitoxin systems.
The regulation of toxin–antitoxin systems. From Ostyn et al. (2025).

 

How microbial community interactions affect toxin-antitoxin systems

Interactions within microbial communities, such as natural competence—the ability of bacteria to take up foreign DNA—can modulate toxin-antitoxin systems. For example, Haemophilus influenzae upregulates the toxin-antitoxin system ToxTA during competence, suggesting its role in regulating DNA acquisition.

Furthermore, toxin-antitoxin systems provide a defense against bacteriophage infections. In Escherichia coli and Vibrio cholerae, phage invasion can trigger transcriptional arrest, leading to antitoxin degradation. This activates the toxin, which subsequently inhibits viral replication.

Also some bacteria in biofilms regulate the formation and dispersal of the biofilm matrix through toxin-antitoxin systems. In Caulobacter crescentus, for example, ParDE4 induces cell death, thereby releasing DNA to reinforce the biofilm matrix.

 

Host immune systems impact toxin-antitoxin systems

When bacteria infect animals or humans, they encounter immune defenses such as acidic environments, oxidative stress, and nutrient deprivation within immune cells. These stressors can activate toxin-antitoxin systems in several bacterial species.

For instance, in Staphylococcus aureus, acidic and oxidative stress reduces antitoxin levels through transcriptional repression or degradation, activating the toxin and potentially contributing to immune cell damage.

In Pseudomonas aeruginosa, antimicrobial peptides from the host can trigger increased toxin expression, helping the bacteria evade immune responses. Also in Salmonella, intracellular acidification and nutrient deprivation, as experienced in immune cells, upregulate multiple toxin-antitoxin systems, promoting bacterial persistence.

Impact of antibiotics and xenobiotics on toxin-antitoxin systems

Antibiotic resistance is a major public health threat. Toxin-antitoxin systems can contribute to this threat by inducing a dormant, low-metabolic state in bacteria, so-called persister cells.

For example, several DNA-damaging antibiotics, like ciprofloxacin, activate toxin-antitoxin systems which promote the “persister lifestyle”. Ultimately, this helps bacteria evade the effects of antibiotics.

Recent studies also suggest that toxin-antitoxin systems may be triggered by nanomaterials and non-antibiotic drugs. This suggests that toxin-antitoxin systems may play even broader roles in stress adaptation.

That’s why better understanding how these sophisticated genetic modules are regulated could provide potential targets for novel antibiotics or therapies that prevent resistance or biofilm formation. This could also include treatments of persistent and hard-to-eradicate bacterial infections.

 

About the author

Marie-Laure Pinel-Marie is a senior Assistant Professor in Biochemistry and Molecular Biology at the University of Rennes, France. Her research focuses on understanding how bacteria adapt to their environment and the molecular mechanisms that drive this adaptation, studying toxin-antitoxin (TA) systems. She has developed strong expertise in the functional characterization of bacterial RNAs, as well as microRNAs in eukaryotic systems, and in designing genetic tools to investigate molecular regulatory mechanisms. Her research combines molecular biology, genetics, microbiology, biochemistry, cell biology, and toxicology approaches.

About this blog section

The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.

Do you want to be a guest contributor?
The #FEMSmicroBlog welcomes external bloggers, writers and SciComm enthusiasts. Get in touch if you want to share your idea for a blog entry with us!

Back to top

Leave a Reply

Your email address will not be published. Required fields are marked *

Share this news