Scientists have identified a novel antibiotic known as Clovibactin, which originates from a specific soil bacterium. The compound presents a distinct method of action against bacterial cell walls, rendering it a promising agent in the fight against antibiotic-resistant “superbugs.” However, its journey toward commercialization necessitates additional studies.
A collaborative effort involving the University of Bonn, the United States, and the Netherlands has elucidated clovibactin’s modus operandi.
The growing prevalence of antibiotic-resistant bacterial pathogens is causing concern. Existing medications are increasingly at risk of becoming obsolete in treating infectious diseases. Consequently, there is an intensified global effort to discover new effective compounds.
A team of researchers from the University of Bonn, the German Center for Infection Research (DZIF), Utrecht University in the Netherlands, Northeastern University in Boston, USA, and NovoBiotic Pharmaceuticals in Cambridge, USA, have successfully identified and understood the mechanism of action of Clovibactin. This new antibiotic is derived from a soil bacterium and demonstrates remarkable efficacy against bacterial cell walls, including those of numerous antibiotic-resistant “superbugs.” The findings have been published recently in the esteemed journal, Cell.
Prof. Dr. Tanja Schneider, of the Institute for Pharmaceutical Microbiology at the University of Bonn and the University Hospital Bonn, stated, “There is an urgent need for new antibiotics to outpace bacteria that have developed resistance.” She noted that very few new substances have been introduced in recent years to counter bacterial pathogens.
Clovibactin displays unique properties compared to existing antibiotics, according to a co-spokesperson of the Transregional Collaborative Research Center “Antibiotic CellMAP.” The Institute for Pharmaceutical Microbiology, in collaboration with the German Center for Infection Research, specializes in unraveling the mechanisms by which potential antibiotics operate.
The soil bacterium from which Clovibactin is derived, known as Eleftheria terrae subspecies carolina, was isolated from a soil sample in North Carolina, USA. It produces Clovibactin to defend itself against rival bacteria. “Clovibactin uniquely attacks multiple sites on the bacterial cell wall by inhibiting vital building blocks,” explains Tanja Schneider. The compound exhibits high-affinity binding to these building blocks, effectively killing the bacteria by rupturing their cellular envelope.
Research teams across various disciplines and countries collaborated to understand the compound’s precise mechanism. Utilizing the iCHip device, the team led by Prof. Kim Lewis of Northeastern University and NovoBiotic Pharmaceuticals succeeded in culturing bacteria that were previously deemed unculturable, thus enabling the discovery of Clovibactin. Dallas Hughes, Ph.D., president of NovoBiotic Pharmaceuticals, LLC, mentioned that the antibiotic has shown high efficacy against a wide range of bacterial pathogens and has proven successful in preclinical mouse studies.
The mode of action of Clovibactin was further clarified by Tanja Schneider’s team. They discovered that Clovibactin selectively and specifically binds to pyrophosphate groups in bacterial cell walls. Detailed structural analyses were performed using solid-state NMR spectroscopy by Prof. Markus Weingarth’s group at Utrecht University in the Netherlands. These studies revealed that Clovibactin encloses its target structure much like a cage, which is reflected in its name, derived from the Greek word “Klouvi.”
Clovibactin primarily targets gram-positive bacteria, including MRSA and tuberculosis-causing bacteria, affecting millions globally. Tanja Schneider expressed optimism about Clovibactin’s resilience to bacterial resistance. After binding to target structures, Clovibactin forms filamentous structures that envelop and further impair bacterial targets. It also stimulates the release of enzymes known as autolysins, which degrade the bacterial cell envelope. “The multiple mechanisms contribute to its remarkable resistance to bacterial countermeasures,” Tanja Schneider noted.
The collaborative effort was essential in achieving this breakthrough, according to Prof. Markus Weingarth. The research team now aims to enhance Clovibactin’s effectiveness, although its commercial availability still requires extensive research, as per Tanja Schneider.
The project received funding from the German Center for Infection Research and the Transregional Collaborative Research Center “Antibiotic CellMAP” of the German Research Foundation, covering the Bonn and Tübingen sides of the collaboration.
Table of Contents
Frequently Asked Questions (FAQs) about Clovibactin
What is Clovibactin?
Clovibactin is a newly discovered antibiotic derived from a soil bacterium. It has shown promise in combating antibiotic-resistant bacteria, commonly known as “superbugs.”
Who is involved in the research on Clovibactin?
The research involves a collaborative effort from the University of Bonn, the German Center for Infection Research, Utrecht University in the Netherlands, Northeastern University in Boston, USA, and NovoBiotic Pharmaceuticals in Cambridge, USA.
What makes Clovibactin unique compared to existing antibiotics?
Clovibactin has a distinct mechanism of action against bacterial cell walls, allowing it to effectively combat antibiotic-resistant bacteria. It binds to vital building blocks of the bacterial cell wall with high specificity and affinity, thereby destroying the bacterial cell envelope.
Where was the soil bacterium found from which Clovibactin is derived?
The soil bacterium, known as Eleftheria terrae subspecies carolina, was isolated from a soil sample collected in the U.S. state of North Carolina.
What is the current stage of research on Clovibactin?
The research is still in its early stages. Although the antibiotic has demonstrated efficacy against a broad spectrum of bacterial pathogens in preclinical mouse studies, further research is required before it can be commercially available.
How was Clovibactin discovered?
The compound was discovered using the iCHip device, which allows for the culturing of previously unculturable bacteria. This has enabled researchers to explore new therapeutic compounds derived from such bacteria.
What is the likelihood of bacteria developing resistance to Clovibactin?
Based on current research, there is optimism that bacterial resistance to Clovibactin will develop more slowly compared to existing antibiotics. This is attributed to its unique mechanism that attacks multiple sites on bacterial cell walls.
Are there any plans to commercialize Clovibactin?
While the research indicates promising results, commercialization requires further studies. The research team is planning to use its findings to enhance the effectiveness of Clovibactin, but it has not yet reached the market.
Who funded the Clovibactin research project?
The project has received funding from the German Center for Infection Research and the Transregional Collaborative Research Center “Antibiotic CellMAP” of the German Research Foundation.
What are the implications of this discovery for the future of antibiotic research?
The discovery of Clovibactin underscores the potential that exists within the natural diversity of bacteria for finding new antibiotics. It serves as a pivotal step in combating antibiotic resistance, one of the most pressing public health issues.
More about Clovibactin
- University of Bonn Official Website
- German Center for Infection Research
- Utrecht University Research
- Northeastern University Antimicrobial Discovery Center
- NovoBiotic Pharmaceuticals
- Journal Cell where the research was published
- Transregional Collaborative Research Center “Antibiotic CellMAP”
- German Research Foundation
- DOI Link to the Published Study
