Antibacterial compounds against non-growing and intracellular bacteriaVisa övriga samt affilieringar
2025 (Engelska)Ingår i: npj Antimicrobials and Resistance, E-ISSN 2731-8745, Vol. 3, nr 1, artikel-id 25Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
Slow- and non-growing bacterial populations, along with intracellular pathogens, often evade standard antibacterial treatments and are linked to persistent and recurrent infections. This necessitates the development of therapies specifically targeting nonproliferating bacteria. To identify compounds active against non-growing uropathogenic Escherichia coli (UPEC) we performed a drug-repurposing screen of 6454 approved drugs and drug candidates. Using dilution-regrowth assays, we identified 39 compounds that either kill non-growing UPEC or delay its regrowth post-treatment. The hits include fluoroquinolones, macrolides, rifamycins, biguanide disinfectants, a pleuromutilin, and anti-cancer agents. Twenty-nine of the hits have not previously been recognized as active against non-growing bacteria. The hits were further tested against non-growing Pseudomonas aeruginosa and Staphylococcus aureus. Ten compounds - solithromycin, rifabutin, mitomycin C, and seven fluoroquinolones-have strong bactericidal activity against non-growing P. aeruginosa, killing >4 log10 of bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, and satraplatin are unique in their ability to selectively target non-growing bacteria, exhibiting poor efficacy against growing bacteria. Finally, 31 hit compounds inhibit the growth of intracellular Shigella flexneri in a human enterocyte infection model, indicating their ability to permeate the cytoplasm of host cells. The identified compounds hold potential for treating persistent infections, warranting further comparative studies with current standard-of-care antibiotics.
Ort, förlag, år, upplaga, sidor
Springer Nature, 2025. Vol. 3, nr 1, artikel-id 25
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Forskningsämne
infektionssjukdomar
Identifikatorer
URN: urn:nbn:se:umu:diva-237918DOI: 10.1038/s44259-025-00097-0OAI: oai:DiVA.org:umu-237918DiVA, id: diva2:1953716
Forskningsfinansiär
Svenska Sällskapet för Medicinsk Forskning (SSMF), PD20-0022Vetenskapsrådet, 2021-06602Vetenskapsrådet, 2021-01146Knut och Alice Wallenbergs Stiftelse, 2020-0037Cancerfonden, 20 0872 PjEuropeiska kommissionen, MIBEst H2020-WIDESPREAD-2018-2020/GA 857518Europeiska kommissionen, MIBEst H2020-WIDESPREAD-2018-2020/GA 8575182025-04-222025-04-222026-03-10Bibliografiskt granskad