ArticleResearch square2025
De Novo Design of Miniprotein Inhibitors of Bacterial Adhesins.
Adam Chazin-Gray, Tuscan Thompson, Edward Lopatto, Pearl Magala, Patrick Erickson, Andrew Hunt, Anna Manchenko, Pavel Aprikian, Veronika Tchesnokova, Irina Basova and 20 more
Abstract readPreprint
In one paragraphArticle in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
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0citing papers in PubMed
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What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registryThe trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
30 authors.
Adam Chazin-GrayUniversity of Washington.
Tuscan ThompsonUniversity of Washington.
Pearl MagalaUniversity of Washington.
Patrick EricksonUniversity of Washington.
Andrew HuntUniversity of Washington.
Anna ManchenkoUniversity of Washington.
Pavel AprikianUniversity of Washington.
Veronika TchesnokovaUniversity of Washington.
Irina BasovaUniversity of Washington.
Denise SanickWashington University in St. Louis.
Kevin TamadonfarWashington University School of Medicine.
Jerome PinknerWashington University School of Medicine.
Karen DodsonWashington University School of Medicine.
Alex KangUniversity of Washington.
Emily JoyceUniversity of Washington.
Asim BeraUniversity of Washington.
Aaron SchmitzWashington University in St. Louis.
Gianluca InterlandiUniversity of Washington.
Mark CartwrightHarvard University.
Andyna VernetHarvard University.
Sarai BardalesHarvard University.
Desmond WhiteHarvard University.
Evgeni SokurenkoUniversity of Washington.
Scott HultgrenDepartment of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine.ORCID 0000-0001-8785-564X Funding
X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Vivian Stojanoff · 2019 to 2026
$38.6MUser Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2MUser Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Gregory L Hura · 2017 to 2026
$28.6MRational design and synthesis of small molecule inhibitors targeting unique pathogenic mechanisms in Gram- and Gram+ bacteria important in UTIU19AI157797 · NIAID · WASHINGTON UNIVERSITY · PI HULTGREN, SCOTT J. · 2021 to 2025
$11.4MCHAPERONE-ASSISTED PILI ASSEMBLY IN PATHOGENIC E. COLIR01AI029549 · NIAID · WASHINGTON UNIVERSITY · PI HULTGREN, SCOTT J., YUAN, PENG · 1991 to 2023
$5.7MAllosteric adhesins of enterobacterial pathogensR01AI171570 · NIAID · UNIVERSITY OF WASHINGTON · PI Rachel E Klevit, EVGENI Veniaminovic SOKURENKO · 2022 to 2026
$3.5MPathogenic Fiber Formation in Bacteria: Structural BasisR37AI048689 · NIAID · WASHINGTON UNIVERSITY · PI SCOTT J. HULTGREN · 2021 to 2026
$2.9MInvestigating Novel Methods to Combat Urinary Tract InfectionsK99GM141364 · NIGMS · UNIVERSITY OF WASHINGTON · PI MAGALA, PEARL · 2022 to 2023
$225kNovel therapeutics for treatment of catheter-associated UTI and depletion of the vaginal reservoirF30DK135390 · NIDDK · WASHINGTON UNIVERSITY · PI TIMM, MORGAN ROSE WILT · 2023 to 2025
$123kNIAID NIH HHS R01 AI029549NIAID NIH HHS R01 AI171570NIAID NIH HHS R37 AI048689NIAID NIH HHS U19 AI157797NIDDK NIH HHS F30 DK135390NIGMS NIH HHS K99 GM141364NIGMS NIH HHS P30 GM124165NIGMS NIH HHS P30 GM124169NIGMS NIH HHS P30 GM133893
6 · The paper itselfAbstract
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 Abp 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 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 murine models of uncomplicated and catheter-associated UTIs in vivo.
Identifiers
PMID41282098
PMCPMC12637805
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