A groundbreaking study led by Federico Iovino, an associate professor and research group leader at the Department of Neuroscience, Karolinska Institutet, has revealed that the endolysin cpl-1 can effectively cross the blood-brain barrier (BBB). This groundbreaking finding holds tremendous promise in the war against bacteria resistance. Even more alarming is that this issue is compromising the effectiveness of antibiotics used to treat serious infections such as meningitis. The findings of this study, with Niels Vander Elst as the first author, were published with DOI: 10.1186/s10020-025-01226-1.
This research addresses the critical issue of antibiotic resistance. It illustrates our growing failure to treat infections with the antibiotics we’ve long relied on. Bacterial resistance impacts the ability of antibiotics to successfully fight infectious disease. Both beta-lactam, like penicillin, and macrolide, like erythromycin, antibiotics fail to treat life-threatening systemic infections as a consequence. This paradoxical effect is particularly concerning in meningitis infections. Timely and effective treatment is often the difference between life and death for the patients that survive.
The Role of Endolysin cpl-1
Endolysin cpl-1 is a remarkable enzyme which has demonstrated potent activity in delivering protection against infections. During the study, it was shown that endolysin cpl-1 on its own was able to provide protection when traditional antibiotics could not. Remarkably, when penicillin was trialed in the context of antibiotic resistance, it offered no protective benefit. This discovery highlights the promise of endolysin cpl-1 as a potent new bactericidal weapon against resistant strains of bacteria.
Even more importantly, the ability of endolysin cpl-1 to permeate the blood-brain barrier further adds to the importance of its application. The blood-brain barrier acts as a gatekeeper to the central nervous system. This polypharmacy barrier has created a formidable challenge for many new drugs to penetrate and reach their therapeutic targets. Endolysin cpl-1 is able to do just that! This new capability advances innovative therapies for life-threatening infections that impact the central nervous system including brain and spinal cord.
Future Directions in Research
Federico Iovino’s group wants to follow up by testing cpl-1’s effectiveness against different varieties of resistant bacteria. This research is a continuation of our work to deepen our knowledge surrounding endolysins. We hope to unlock their promise not just against the pathogens that cause meningitis, but other SBI that pose deadly public health burdens.
The implications of this research go beyond short term clinical use. By pinpointing the most effective and strategic endolysin-based therapies, researchers seek to arm healthcare workers with innovative approaches in the ongoing battle against antibiotic-resistant bacteria. With resistance rising across the entire world, it is all the more important to identify novel innovative solutions. These technical innovations will assist with providing access to safe and effective treatment choices for patients fighting deadly infections.