9q1h
A7 minibinder in complex with Abp2D
Structural highlights
FunctionPublication Abstract from PubMedThe 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 recognition of host receptors, block biofilm formation, and are effective in treating and preventing uncomplicated and catheter-associated UTIs in vivo. Targeting virulence factors outside the cell membrane with protein design provides a rapid route to next-generation therapeutics that can disrupt pathogenesis and thus are capable of treating and preventing disease in an antibiotic-sparing manner. De Novo Design of Miniprotein Inhibitors of Bacterial Adhesins.,Chazin-Gray AM, Thompson TR, Lopatto EDB, Magala P, Erickson PW, Hunt AC, Manchenko A, Aprikian P, Tchesnokova V, Basova I, Sanick DA, Tamadonfar KO, Timm MR, Pinkner JS, Dodson KW, Kang A, Joyce E, Bera AK, Schmitz AJ, Ellebedy AH, Hvorecny KL, Cartwright MJ, Vernet A, Bardales S, White D, Klevit RE, Sokurenko EV, Hultgren SJ, Baker D bioRxiv [Preprint]. 2025 Aug 18:2025.08.18.670751. doi: , 10.1101/2025.08.18.670751. PMID:40894640[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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