A new hypothesis concerning a crucial step in the anthrax infection process has been advanced by scientists at the National Institute of Standards and Technology (NIST) and the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) at Fort Detrick, Md.
The research teams have explored the behavior of the toxins that rapidly overwhelm the body as the often-fatal disease progresses. Their findings suggest a new possible mechanism by which anthrax bacteria deliver the protein molecules that poison victims. Anthrax is easily weaponized; the findings could help lead to a more effective cure.
Anthrax bacteria kill by releasing three toxins that work in concert to destroy cells. One toxin, called PA, attaches to the cell membrane, where its surface serves as a sort of landing pad for the other two toxins, called LF and EF. Once several molecules of LF and EF have latched onto PA, the cell membrane tries to destroy these unwanted hangers-on by wrapping them up in an "endosome," a small bubble of membrane that gets pinched off and moved into the cell's interior. There, the cell attempts to destroy its contents by a process that includes making the interior of the endosome more acidic. But before the cell can fully carry out its plan, the LF and EF escape from the endosome and wreak havoc in the cell's interior. The question is: how do these toxins escape?
"A recent hypothesis is that LF and EF completely unfold and then squeeze through the narrow hole that PA forms in the endosomal membrane," says NIST physical scientist John Kasianowicz. "However, the studies used to support this concept make use of short segments of the toxins, not their native full-length versions. The results don't show that the complete LF and EF are transported through the pore or whether they refold into functional enzymes once they reach the other side. So, we decided to look at other possible explanations."
The NIST/USAMRIID team explored the behavior of full-length toxins using an artificial membrane that mimics a cell's exterior. They put the toxins mixed in salt water on one side of this barrier and slowly rendered this fluid more acidic, resembling conditions within an endosome. But the change in chemistry apparently altered the physical characteristics of the LF and EF toxins, because it caused them to bind irreversibly to the PA pore, creating a "complex" of multiple toxins. This result alone suggested it would be difficult, if not impossible, for LF and EF to thread through the pore.
In addition, the team discovered that the bound toxins tend to rupture membranes. This finding led them to suggest that perhaps it is complexes of LF or EF bound to PA that gets into cells, and that these complexes are the active toxins inside cells.
Kasianowicz says this new hypothesis could explain previous experimental results, in which the complex was found in the blood of animals that died of anthrax. But he emphasizes that the matter is not yet settled.
"We don't know enough to choose between these theoriesand in fact it's possible that the toxins escape the endosome by more than one mechanism," he says. "But it's important that we better understand this step in the process to thwart anthrax more effectively."
Reference: Nablo BJ, et al.  Anthrax toxin-induced rupture of artificial lipid bilayer membranes. Journal of Chemical Physics, Aug. 8, 2013 (Vol.139, Issue 6), DOI: 10.1063/1.4816467
Â
Stay prepared and protected with Infection Control Today's newsletter, delivering essential updates, best practices, and expert insights for infection preventionists.
Breaking the Cycle of Silence: Why Sharps Injuries Go Unreported and What Can Be Done
Published: July 24th 2025 | Updated: July 23rd 2025Despite decades of progress in health care safety, a quiet but dangerous culture still lingers: many health care workers remain afraid to report sharps injuries, fearing blame more than the wound itself.
US Withdrawal From UNESCO Signals a Dangerous Step Back for Global Science
July 22nd 2025In a decision heavy with consequence and light on foresight, the US has once again chosen to walk away from UNESCO, leaving behind not just a seat at the table, but a legacy of global scientific leadership that now lies in question.
Pathogen Pulse: Facilities Need the SPD, Yersinia Enterocolitica Outbreak, and More
July 22nd 2025From unsterilized surgical tools in Colorado to a years-long methicillin-resistant Staphylococcus aureus (MRSA) outbreak in Virginia and a surging measles crisis in Canada, recent headlines reveal the fragile front lines of infection prevention and the high stakes when systems fail.
Telemedicine's Transformative Role in PPE Distribution and Sterile Equipment Management
July 22nd 2025In an era defined by digital transformation and post-pandemic urgency, telemedicine has evolved beyond virtual visits to become a vital infrastructure for delivering personal protective equipment (PPE) and managing sterile supplies. By enabling real-time forecasting, remote quality control, and equitable distribution, telemedicine is revolutionizing how health care systems protect both patients and providers.
Reducing Hidden Risks: Why Sharps Injuries Still Go Unreported
July 18th 2025Despite being a well-known occupational hazard, sharps injuries continue to occur in health care facilities and are often underreported, underestimated, and inadequately addressed. A recent interview with sharps safety advocate Amanda Heitman, BSN, RN, CNOR, a perioperative educational consultant, reveals why change is overdue and what new tools and guidance can help.