Conformational plasticity across phylogenetic clusters of RND multidrug efflux pumps and its impact on substrate specificity.

ABSTRACT: Antibiotic efflux plays a key role for the multidrug resistance in Gram-negative bacteria^1-3. Multidrug efflux pumps of the resistance nodulation and cell division (RND) superfamily function as part of cell envelope spanning systems and provide resistance to diverse antibiotics^4,5. Here, we identify two phylogenetic clusters of RND proteins with conserved binding pocket residues. Based on the characterisation of one representative of each cluster, K. pneumoniae OqxB and E. coli AcrB, we show that the transfer of a single conserved residue between both clusters alters the resistance against a panel of structurally unrelated drugs. The substitution is not only associated with changes in the binding pocket architecture, but also alters the equilibrium betwe

SUBMITTER: Lazarova M 

PROVIDER: S-EPMC11601597 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature