Scientists from the Scripps Research Institute have discovered the key chemical that signals Bacillus anthracis, the bacterium that causes anthrax, to become lethal. This finding opens up new avenues of exploration for the development of treatments for bacterial infections. The study was published in the Nov. 21 edition of the journal PLoS Pathogens.
The Scripps Research scientists identified bicarbonate, a chemical found in all body fluids and organs that plays a major role in maintaining pH balance in cells, as providing the signal for Bacillus anthracis to unleash virulence factors. Without the presence of the bicarbonate transporter in the bloodstream, the scientists found, the bacteria do not become virulent.
Scientists have known for some time that bicarbonate is implicated in many diseases, but controversy has existed about whether bicarbonate, carbon dioxide, or some combination of these two molecules are responsible for triggering bacterial pathogenesis. This study confirms, for the first time, that it is indeed bicarbonate, rather than carbon dioxide, that signals the gram-positive B. anthracis to become virulent. This finding also is significant because other pathogenic bacteria such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera have bicarbonate transport pathways similar to B. anthracis and thus are likely to have similar virulence triggering mechanisms.
Gram-positive bacteria are the major culprits driving the increase of community and hospital acquired bacterial infections. The Centers for Disease Control and Prevention (CDC) estimates that as many as 10 percent of all patients, or about 2 million people, contract hospital-acquired infections each year. These bacteria are often resistant to multiple antibiotics, making the problem a growing public health concern and the need for new antibacterial treatment more urgent. Now, the bicarbonate transporter pathway may be investigated as a potential new target for drug intervention.
"How a bacterium recognizes signals in the host that trigger pathogenesis mechanisms, and the nature of the mechanisms necessary to develop pathogenesis, remain poorly understood," said Scripps Research associate professor Marta Perego, PhD, who conducted the study with Scripps Research postdoctoral fellow Adam Wilson, PhD, and colleagues. "We have identified an essential component for the induction of virulence gene expression in response to host bicarbonate levels and have used this finding to learn more about the extracellular and intracellular signals controlling virulence."
Perego's latest discovery builds on her lab's expertise in the study of bacterial virulence signaling and in the regulatory networks responsible for pathogenicity in other gram-positive bacteria. Her interest in bicarbonate transport pathways as bacteria virulence signaling mechanisms grew out of an early observation that growth of B. anthracis in carbon dioxide and sodium bicarbonate strongly induced toxin production in the laboratory setting. The mechanism behind this observation, however, was never uncovered.
"It was observed that the best medium for toxin production was one that people believed mimicked conditions found in the blood of a human or animal host, where anthrax bacteria would find both carbon dioxide and bicarbonate. But we've never known which of these two molecules was the more important for bacterial pathogenesis, and whether this belief was correct," Perego said. "Now, we know that it is bicarbonate and that the growth in the presence of bicarbonate really mimics the host growth conditions."
In its current study, the Perego lab identified a previously unknown ATP-binding cassette transporter (ABC-transporter)—which is identified by the gene number BAS2714-12—that was shown to be essential to transporting bicarbonate. As a group, ABC-transporters use the energy of ATP hydrolysis to transport various substrates across cellular membranes. In this case, when the genes that code for the BAS2714-12 ABC transporter were deleted, the rate of bicarbonate uptake inside the cell greatly decreased, induction of toxin gene expression did not occur, and virulence in an animal model of infection was abolished. Elimination of carbon dioxide production within the bacterial cell had no effect on toxin production, suggesting that CO2 activity is not essential to virulence factor induction and that bicarbonate, not CO2, is the signal essential for virulence induction.
"In light of these findings, investigation of bicarbonate regulation and transport should be of much greater significance to a large number of pathogenic organisms," Perego said.
In addition to Perego and Wilson, the other authors of "The bicarbonate transporter is essential for Bacillus anthracis lethality" were Magali Soyer and James Hoch, PhD, head of the Division of Cellular Biology and Professor in the Department of Molecular and Experimental Medicine at The Scripps Research Institute.
This study was supported by the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, the National Institutes of Health, and the Stein Beneficial Trust.
Stay prepared and protected with Infection Control Today's newsletter, delivering essential updates, best practices, and expert insights for infection preventionists.
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.
New Study Explores Oral Vancomycin to Prevent C difficile Recurrence, But Questions Remain
July 17th 2025A new clinical trial explores the use of low-dose oral vancomycin to prevent Clostridioides difficile recurrence in high-risk patients taking antibiotics. While the data suggest a possible benefit, the findings stop short of statistical significance and raise red flags about vancomycin-resistant Enterococcus (VRE), underscoring the delicate balance between prevention and antimicrobial stewardship.
What Lies Beneath: Why Borescopes Are Essential for Verifying Surgical Instrument Cleanliness
July 16th 2025Despite their smooth, polished exteriors, surgical instruments often harbor dangerous contaminants deep inside their lumens. At the HSPA25 and APIC25 conferences, Cori L. Ofstead, MSPH, and her colleagues revealed why borescopes are an indispensable tool for sterile processing teams, offering the only reliable way to verify internal cleanliness and improve sterile processing effectiveness to prevent patient harm.
The Next Frontier in Infection Control: AI-Driven Operating Rooms
Published: July 15th 2025 | Updated: July 15th 2025Discover how AI-powered sensors, smart surveillance, and advanced analytics are revolutionizing infection prevention in the OR. Herman DeBoard, PhD, discusses how these technologies safeguard sterile fields, reduce SSIs, and help hospitals balance operational efficiency with patient safety.
Targeting Uncertainty: Why Pregnancy May Be the Best Time to Build Vaccine Confidence
July 15th 2025New national survey data reveal high uncertainty among pregnant individuals—especially first-time parents—about vaccinating their future children, underscoring the value of proactive engagement to strengthen infection prevention.