9FM0

Human antibody (Fab) and P. aeruginosa (T3SS) protein PcrV-fragment complex

Summary for 9FM0

• Entry DOI: 10.2210/pdb9fm0/pdb
• Descriptor: Human Fab Heavy Chain (FabHC) V-region, Human Fab Light Chain (FabLC) V-region, Type III secretion protein PcrV, ... (6 entities in total)
• Functional Keywords: human antibodies, type iii secretion system, pcrv, virulence, pseudomonas, bacterial infection, antimicrobials, anti-virulence, mab, amr, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 123635.24

Authors

Desveaux, J.M.,Contreras Martel, C.,Dessen, A. (deposition date: 2024-06-05, release date: 2025-06-18, Last modification date: 2026-03-04)

Primary citation

Desveaux, J.M.,Faudry, E.,Contreras-Martel, C.,Cretin, F.,Dergan-Dylon, L.S.,Amen, A.,Bally, I.,Tardivy-Casemajor, V.,Chenavier, F.,Fouquenet, D.,Caspar, Y.,Attree, I.,Dessen, A.,Poignard, P.
Neutralizing human monoclonal antibodies that target the PcrV component of the type III secretion system of Pseudomonas aeruginosa act through distinct mechanisms.
Elife, 14:-, 2026

PubMed Abstract: is a major human opportunistic pathogen associated with a high incidence of multi-drug resistance. The antibody-based blockade of virulence factors represents a promising alternative strategy to mitigate its infectivity. In this study, we employed single B cell sorting from cystic fibrosis patients to isolate human monoclonal antibodies (mAbs) targeting proteins from the Type 3 Secretion System (T3SS) and characterized a panel of mAbs directed at PscF and PcrV. Among those, two mAbs, P5B3 and P3D6, that bind to the injectisome tip protein PcrV, exhibited T3SS blocking activity. We solved the crystal structure of the P3D6 Fab-PcrV complex, which revealed that the Ab binds to the C-terminal region of PcrV. In addition, we compared the T3SS-blocking activity of three PcrV-targeting mAbs, including two from previous independent studies, using two distinct assays to evaluate pore formation and toxin injection. We conducted a mechanistic and structural analysis of their modes of action through modeling based on the known structure of a functional homolog, SipD from . The analysis suggests that anti-PcrV mAbs may act through different mechanisms, ranging from preventing PcrV oligomerization to disrupting PcrV's scaffolding function, thereby inhibiting the assembly and function of the translocon pore. Our findings provide additional evidence that T3SS-targeting Abs, some capable of inhibiting virulence, are elicited in -infected patients. The results offer deeper insights into PcrV recognition by mAbs and their associated mechanisms of action, helping to identify which Abs are more likely to be therapeutically useful based on their mode of action and potency. This paves the way for the development of effective alternatives to traditional antibiotics in the fight against this resilient pathogen.

PubMed: 41700594
DOI: 10.7554/eLife.105195

Experimental method

X-RAY DIFFRACTION (2.56 Å)