<i>De Novo</i> Design of Miniprotein Inhibitors of Bacterial Adhesins.

ABSTRACT: The rise of multidrug-resistant bacterial infections necessitates the discovery of novel antimicrobial strategies. Here, we show that protein design provides a generalizable means of generating new antimicrobials by neutralizing the function of bacterial adhesins, which are virulence factors critical in host-pathogen interactions. We de novo designed high-affinity miniprotein binders to FimH and Abp1D/Abp2D chaperone usher pili adhesins from uropathogenic Escherichia coli and Acinetobacter baumannii, respectively, which are implicated in mediating both uncomplicated and catheter-associated urinary tract infections (UTI) responsible for significant morbidity and mortality worldwide. The designed antagonists have high specificity and stability, disrupt bacterial recognit

SUBMITTER: Chazin-Gray AM 

PROVIDER: S-EPMC12393372 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature