New potentiators of ineffective antibiotics: Targeting the Gram-negative outer membrane to overcome intrinsic resistance

Because of the rise in antibiotic resistance and the dwindling pipeline of effective antibiotics, it is imperative to explore avenues that breathe new life into existing drugs. This is particularly important for intrinsically resistant Gram-negative bacteria, which are exceedingly difficult to treat. The Gramnegative outer membrane (OM) prevents the entry of a plethora of antibiotics that are effective against Gram-positive bacteria, despite the presence of the targets of these drugs. Uncovering molecules that increase the permeability of the OM to sensitize Gram-negative bacteria to otherwise ineffective antibiotics is an approach that has recently garnered increased attention in the field. In this review, we survey chemical matter which has been shown to potentiate antibiotics against Gramnegative bacteria by perturbing the OM. These include peptides, nanoparticles, macromolecules, antibiotic conjugates, and small molecules.

Automated summary

With the rise of antibiotic resistance and the dwindling pipeline of effective antibiotics, it is crucial to find ways to revitalize existing drugs. Perturbing the outer membrane to enhance the susceptibility of Gram-negative bacteria to antibiotics has recently gained increased attention in the field, offering a potential new avenue for combating antibiotic resistance.