Research has revealed 29 new antibodies that target the bacterium Klebsiella pneumoniae, which is a significant contributor to drug-resistant infections. Through a combination of genetic and functional techniques, the scientists were able to decipher how these antibodies engage with the antigens located on the bacteria’s surface. Additionally, they discovered that several of these newly identified antibodies work together to neutralize this pathogen.
Research conducted at UMC Utrecht has uncovered 29 new antibodies that target the bacterium Klebsiella pneumoniae, which is a major factor in drug-resistant infections. By employing genetic and functional methods, the research team also figured out how these antibodies connect with antigens found on the bacterial surface. Furthermore, they found that some of these new antibodies can synergistically work together to neutralize this pathogen.
The rise of antimicrobial resistance (AMR) is a critical issue that necessitates the creation of alternative treatments for bacterial infections. A promising method involves enhancing the immune response through antibodies, whether by means of vaccination or direct treatment with therapeutic antibodies. One key way antibodies can eliminate bacteria is by activating the complement system when they bind to surface antigens of bacteria. This complement activation can lead to the destruction of bacteria by forming large pores in their membranes and facilitating phagocytosis. Nonetheless, the specific mechanisms of how antibodies kill bacteria via complement activation are still not well understood. Moreover, there is an ongoing need for new techniques to identify antibacterial antibodies and thoroughly investigate their interactions with bacterial surface elements. Prof. Suzan Rooijakkers and her team from the Department of Medical Microbiology at UMC Utrecht developed an innovative method to identify new antibacterial antibodies from human memory B cells.
Newly Discovered Antibodies
While it is typical to label B cells with purified antigens, the researchers chose a broader method by staining B cells with whole living bacteria, helping to preserve the natural context of the antigens. This approach successfully led to the identification of 29 unique antibodies against the opportunistic pathogen Klebsiella pneumoniae, which is notably responsible for hospital-acquired infections with rising levels of antimicrobial resistance. The team found that certain antigens on the bacterial surface played a crucial role in determining the antibodies’ ability to activate the complement system and kill bacteria. Additionally, studies of antibody mixtures indicated that some antibodies could enhance one another’s attachment to the bacterial surface, acting synergistically.
Principal investigator Suzan Rooijakkers, who is also a Professor of Microbiology at UMC Utrecht, remarked: “We believe that our innovative approach will speed up the discovery of monoclonal antibodies against bacterial pathogens. Furthermore, our research will encourage more exploration of whether combinations of antibodies could offer a viable path toward developing effective antibody-based treatments for challenging infections.”
