Superbugs are drug-resistant microbes causing about 700,000 deaths annually, potentially rising to 10 million by 2050. Pseudomonas aeruginosa is a major hospital-acquired multidrug resistant pathogen, especially dangerous for immunocompromised patients. The World Health Organization lists it as a critical priority pathogen, highlighting the urgent need for new drug targets and therapies.
Because of its key role in bacterial infection, the Type III Secretion System (T3SS) represents a major therapeutic target of P. aeruginosa. In particular, the injectisome « tip » protein PcrV is especially promising, as targeting it alone can effectively block T3SS activity and virulence both in vitro and in vivo.
Three groups from IBS (PatBac, PB&RC and CAID) teamed together to explore human antibody (humAb) repertoire in chronically-infected cystic fibrosis patients from the CHU Grenoble, aiming to generate humAbs able to block bacterial infectivity. The approach, based on single memory B cell sorting from patients and a mAb production and screening pipeline, yielded two humAbs capable of binding PcrV and blocking toxin delivery into host cells.
Combining cellular microbiology, genetics, and structural approaches, the scientists uncovered several mechanisms by which humAbs block T3SS action, opening new avenues for effective therapies to combat antimicrobial resistance.
Neutralizing human monoclonal antibodies that target the PcrV component of the type III secretion system of Pseudomonas aeruginosa act through distinct mechanism. Desveaux JM, Faudry E, Carlos Contreras-Martel C, Cretin F, Dergan-Dylon LS, Amen A, Bally I, Tardivy-Casemajor V, Chenavier F, Fouquenet D, Caspar Y, Attree I*, Dessen A*, Poignard P*. Elife 2026, 14:RP105195. doi : 10.7554/eLife.105195.
*co-corresponding
Contacts :
- Ina Attree (IBS/Bacterial Pathogenesis and Cellular Responses Group)
- Pascal Poignard (IBS/Complement, antibodies and infectious disease Group)