Siderophore Vectors Smuggle Meropenem and an MBL Inhibitor into Resistant Pseudomonas
- Tris-catecholate siderophore–meropenem conjugates overcame porin-loss and efflux-based carbapenem resistance in P. aeruginosa in an iron-dependent manner.
- The team also vectorized an indole-carboxylate MBL inhibitor, which alone barely works in P. aeruginosa, apparently for permeability reasons.
- The conjugates restored inhibitor activity and reversed meropenem and cefiderocol resistance in MBL-producing clinical isolates, in vitro and in a Galleria mellonella model.
💡 Points
Permeability, not target affinity, is what kills most Gram-negative programs, so vectorizing a known but impermeable MBL inhibitor is a smart shortcut. Reversing cefiderocol resistance is the headline for me, since that drug already exploits iron uptake. I'd press on conjugate stability in serum and whether resistance simply migrates to siderophore receptors.