Niels Vander Elst

Over the past seven years, I have specialised in bacteriophage-derived endolysins, which are enzymes with powerful potential to combat antibiotic-resistant infections. This journey began during an internship at Stockholm University and has since evolved into a personal and professional mission to translate the endolysin technology into real-world clinical and veterinary solutions.

My work has consistently focused on Gram-positive pathogens, particularly Streptococcus and Staphylococcus species. This focus has led to multiple high-impact publications in Q1 journals, invited talks at international conferences - including the honour of opening a session on emerging technologies - and several patent applications. One of these patented endolysins is now progressing into clinical trials for a veterinary application, and another was named a finalist for the University of Maryland’s ‘Invention of the Year’ award in 2020.

I managed to secure competitive research funding across Europe and the United States, including a fellowship from the Belgian American Educational Foundation (BAEF), which supported my research at the Institute for Bioscience and Biotechnology Research (University of Maryland). I subsequently completed a dual PhD in Biotechnology and Veterinary Medicine at KU Leuven and Ghent University, funded by the Research Foundation Flanders (FWO) in Belgium. In my current role as a postdoctoral researcher at Karolinska Institutet, I continue to advance the endolysin technology by engineering the next generation of molecules to overcome current limitations, such as mitigating bacterial antigen release upon lysis, improving biodistribution, and developing synergistic combinations with various antibiotic classes. These efforts aim to bring this technology closer to clinical translation and meaningful patient outcomes. A recent study I authored demonstrated that endolysins can restore antibiotic susceptibility in β-lactam- and macrolide-resistant Streptococcus pneumoniae. The study received widespread attention through a press release, with multiple media (TV, Radio) reporting on my study, ranking it firmly in the top 5% of research outputs ever scored by Altmetric. My postdoctoral work also received an award in 2024 at the yearly Encephalitis meeting in London.

Beyond the lab, I am actively involved in academic leadership and education. I was nominated by my peers and elected to the Leadership of the Junior Faculty at Karolinska Institutet, where I help foster a vibrant and inclusive research environment. In this capacity, I also serve as a representative for Junior Faculty on the board of the open science working group. Additionally, I contribute to the medical curriculum at KI, where I am involved in teaching neurohistology to Sweden’s next generation of medical doctors.

I am passionate about science communication and regularly contribute outreach articles to help bring phage-based antimicrobials into the broader public dialogue. My long-term goal is to bridge endolysin innovation and its clinical implementation to deliver effective and accessible antimicrobial strategies, whether the patient is human or animal.

My research focuses on bacteriophage-derived endolysins, being modular enzymes that hydrolyze the peptidoglycan layer of bacterial cell walls, leading to rapid osmotic lysis of Gram-positive pathogens. Due to their ability to lyse bacteria externally when recombinantly produced, endolysins represent a promising alternative to traditional antibiotics, particularly against resistant strains. Additionally, endolysins exhibit strong anti-biofilm activity and can eliminate persister cells, an important advantage in chronic and recurrent infections.

While endolysin research has evolved over the past few decades, the rational engineering of these enzymes has gained momentum only in the last 15 years. Owing to their modular architecture, endolysins can be functionally optimized through domain swapping and fusion design. My PhD research focused on the high-throughput engineering of third-generation endolysin variants with expanded functionality, including intracellular killing capacity against veterinary Streptococcus species, such as S. uberis. This work laid the foundation for the development of endolysins tailored for specific veterinary pahogens in dairy cows, and included the filing of a patent with the engineered compound progressing into clinical trials.

Currently, as a postdoctoral researcher at Karolinska Institutet, I am characterising well-studied pneumococcal endolysins in cell culture and in vivo models, with a specific focus on central nervous system infections. My work aims to overcome current translational barriers by engineering next-generation endolysins that address key limitations such as bacterial antigen release upon lysis, suboptimal pharmacodynamics, and limited penetration across biological barriers. In our most recent study, we demonstrated that endolysins can not only cross the blood-brain barrier but also resensitise β-lactam- and macrolide-resistant Streptococcus pneumoniae to conventional antibiotics. This finding opens the door to combination therapies that extend the lifespan of existing antimicrobials.

Overall, my research combines synthetic biology, protein engineering, and infection biology to advance endolysins toward clinical use in both human and veterinary medicine.

KI Medical Program - Neurohistology