If you're interested in our workflow for producing Pseudomonas aeruginosa type III secretion system-neutralizing monoclonal antibodies from human B cells, a detailed protocol is now available.
Antibiotic-resistant bacteria represent an escalating global threat, impacting not only those affected but also straining entire healthcare systems. In particular, infections with the bacterium Pseudomonas aeruginosa are feared due to numerous resistance mechanisms and can lead to complicated lung and bloodstream infections, especially in critically ill individuals. Furthermore, this pathogen has the capability to colonize organs like the lungs, contributing to progressive tissue damage.
In our study, we explored the potential of isolating and expressing highly neutralizing antibodies from human immune cells - a successful strategy for viral infections - to develop novel therapies for bacterial infections. Our focus was on determining whether this approach, proven effective in viral contexts, could be extended to combat bacterial infections. To identify suitable antibodies, we concentrated on patients with cystic fibrosis, a condition often associated with chronic P. aeruginosa colonization in the lungs. Through screening assays, we identified monoclonal antibodies in the blood samples of certain cystic fibrosis patients capable of neutralizing P. aeruginosa's virulence.
These antibodies operate by blocking a crucial virulence factor of the bacterium—the type III secretion system, which plays an important role especially in severe infections with P. aeruginosa. Extensive experiments involving cell culture and animal models demonstrated that the newly developed antibodies exhibit efficacy comparable to classical antibiotics against the bacterium. Notably, these antibodies, remain effective against highly resistant bacteria, as their activity is independent of the mechanisms employed by conventional antibiotics.
Congrats to Alexandra for winning the poster prize at the annual meeting of the German Center for Infection Research (DZIF) in Hannover! Well done!