Authors: Karin Goldberg, Arseniy Lobov, Paola Antonello, Merav D. Shmueli, Idan Yakir, Tal Weizman, Adi Ulman, Daoud Sheban, Einav Laser, Matthias P. Kramer, Ronen Shteinvil, Guoyun Chen, Angham Ibraheem, Vera Sysoeva, Vered Fishbain-Yoskovitz, Gayatree Mohapatra, Anat Abramov, Sandy Shimshi, Kseniia Ogneva, Madhurima Nandy, Sivan Amidror, Hadar Bootz-Maoz, Shanny H. Kuo, Nili Dezorella, Assaf Kacen, Aaron Javitt, Gee W. Lau, Nissan Yissachar, Zvi Hayouka and Yifat Merbl
Nature, 05 March 2025
Scientists use TEER measurements on Axion BioSystems’ Maestro Z, and other methods, to explore the role of the proteasome and uncover a potential untapped source of natural antibiotics.
Protein degradation via proteasomes plays an important role in immune signaling and antigen presentation; however, most previous research has focused on the degradation process and substrates without considering potential roles for the degradation products. To investigate whether these products may have additional roles in immune signaling or other processes, scientists in this study explored the downstream role of these proteasome-cleaved peptides.
In results that may pave the way to new therapeutics, the authors described a role for proteasome-cleaved peptides in defense against bacterial infection via altered proteasomal function. To assess the activity of proteasome-derived defense peptides (PDDPs), the team used TEER measurements on Axion BioSystems’ Maestro Z analyzer to determine PDDP effects on barrier integrity in vitro. Results demonstrated that bacterial infection with P. aeruginosa, a notoriously antibiotic-resistant bacterium, reduced barrier integrity, which was rescued via treatment with PPP1CB peptide—a PDDP with a relatively long half-life and prominent antimicrobial activity.
Overall, the authors conclude that in addition to identifying mechanistic insights related to the role of the proteasomes, these findings, “could provide an untapped source of natural antibiotics for biotechnological applications and therapeutic interventions in infectious diseases and immunocompromised conditions.”
