Collaboration : Pascal Poignard, CAID group
Antibiotic resistance is one of todays’ major global health threats. Among multi drug resistant (MDR) pathogens, the ESKAPE group of infectious bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp) is of particular importance as they are able to evade the most common antibiotic therapies.
Monoclonal antibodies (mAbs) that target bacterial virulence factors offer highly promising alternative perspectives for antibiotics, due to their high specificity, the absence of cross resistance and possibility of synergy with antibiotics. They also potentially reduce the spred of antibiotic resistance due to limited need for antibiotic use.
Withing the ANR-funded project (HumaBact) we exploit humoral responses of cystic fibrosis patients to infection, together with functional screens and rational structural approaches to isolate therapeutic human mAbs targeting selected virulence factors.
Figure 1 : Two methods for isolation of human mAbs starting from infected individuals.
Using the established pipelines of Abs isolation (Figure 1), we have validated a tip protein of the type III secretion system (T3SS), PcrV, as the first virulence target for mAb-based virulence blocking (https://elifesciences.org/reviewed-preprints/105195v1).
Figure 2 : Evaluation of T3SS virulence inhibition by human mAbs starting from CF patients.
Figure 3 : Different mechanisms of inhibition of effectors injection by monoclonal antibodies anti-PcrV
(All figures are created in https://BioRender.com)