How surroundings influence anthrax bacteria’s ability to create toxins

Greg Howard
4th December, 2025

How surroundings influence anthrax bacteria’s ability to create toxins

The master virulence regulator AtxA directly links carbon metabolism to virulence in B. anthracis by physically interacting with the glucose transporter PtsG and the metabolic enzyme Pyc, an association demonstrated through co-affinity purification (a, b) and confirmed in live cells with fluorescence microscopy (c).

Image adapted from: Bothra et al. / CC BY (Source)

Key Findings

  • Anthrax toxin production is significantly boosted by glucose alongside carbon dioxide, highlighting a key metabolic link to virulence
  • The AtxA protein, crucial for anthrax toxins, physically interacts with PtsG—a glucose transporter—and Pyc, an anaplerotic enzyme, linking metabolism directly to toxin activation
  • Disrupting PtsG or Pyc significantly reduces anthrax toxin production and severely weakens the bacteria’s ability to cause disease in animal models
Anthrax, caused by the bacterium Bacillus anthracis, is a serious infectious disease. Its severity stems from potent toxins and a protective capsule, both controlled by a key regulator called AtxA. Understanding how AtxA functions is crucial for developing new treatments. Researchers at the National Institutes of Health & University of Pittsburgh School of Medicine have recently shed light on the intricate mechanisms governing AtxA’s activity[1]. For years, scientists have known that AtxA controls the production of anthrax toxins and the capsule[2]. It was observed that AtxA regulates genes both on the bacterial chromosome and on plasmids – small, circular DNA molecules – that carry the instructions for making the toxins and capsule. However, the precise way AtxA interacts with these genes remained unclear, and direct evidence of AtxA binding to DNA was lacking. Initial studies suggested AtxA might recognize curved DNA structures[2], but this needed further investigation. It was also discovered that AtxA’s activity is influenced by environmental factors like carbon dioxide (CO2) and glucose[3][4]. The new study builds on these earlier findings, revealing a surprising connection between AtxA and the bacterial glucose metabolism system, known as the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS). The PTS is responsible for transporting glucose into the cell, and it also plays a role in regulating gene expression. Researchers found that deleting the atxA gene not only reduced toxin production but also impaired the bacteria’s ability to take up glucose. This suggested AtxA isn’t just a regulator of the glucose system, but potentially a part of it. The study identified a specific region within AtxA, called the EIIB domain, as critical for its function. Mutating a single amino acid (cysteine at position 402) within this domain abolished AtxA’s ability to activate toxin gene expression. Further investigation revealed that the EIIB domain physically interacts with a protein called PtsG, a key component of the glucose-PTS system. This interaction was confirmed using a technique called FLIM (Fluorescence Lifetime Imaging Microscopy), which allowed researchers to visualize the two proteins binding to each other inside bacterial cells. Importantly, the researchers demonstrated that this physical interaction is essential for AtxA’s activity. By creating versions of AtxA that couldn’t interact with PtsG, they found that the protein lost its ability to activate toxin gene expression. This suggests that PtsG acts as a bridge, transmitting signals from the glucose-PTS system directly to AtxA. Previous work had indicated that phosphorylation – the addition of phosphate groups – within the PTS system influences AtxA activity[3], but the mechanism wasn’t understood. This study clarifies that PtsG is a key player in this process. The synergistic effect of glucose and CO2 on toxin production, previously observed[3], was also investigated. The researchers found that an enzyme called Pyc (pyruvate carboxylase), which regulates the production of phosphoenolpyruvate (PEP) – a molecule central to the PTS system – plays a crucial role. Deleting pyc reduced the combined effect of glucose and CO2 on AtxA activity, confirming that PEP levels are important for enhancing AtxA function. In essence, the study proposes a model where glucose and CO2 influence AtxA activity through a chain of events. Glucose enters the cell via the PTS system, leading to the production of PEP. PEP then initiates a phosphorelay – a transfer of phosphate groups – that ultimately activates AtxA through its interaction with PtsG. This activation then triggers the production of anthrax toxins. This research expands on earlier findings that showed AtxA’s activity is linked to phosphorylation[3], pinpointing the specific proteins and pathways involved. It also clarifies the role of CO2, which appears to influence PEP levels and thus the phosphorelay system.

EnvironmentGeneticsAnimal Science

References

Main Study

1) Environmental regulation of toxin production in Bacillus anthracis

Published 1st December, 2025

https://doi.org/10.1371/journal.ppat.1013587

Related Studies

2) Bacillus anthracis Virulence Regulator AtxA Binds Specifically to the pagA Promoter Region.

https://doi.org/10.1128/JB.00569-19

3) Influence of the phosphoenolpyruvate:carbohydrate phosphotransferase system on toxin gene expression and virulence in Bacillus anthracis.

https://doi.org/10.1111/mmi.14413

4) Glucose-dependent activation of Bacillus anthracis toxin gene expression and virulence requires the carbon catabolite protein CcpA.

https://doi.org/10.1128/JB.01656-09


Related Articles

An unhandled error has occurred. Reload 🗙