RT Journal Article SR Electronic T1 Nitroxoline as a promising alternative drug for the treatment of Lyme disease based on an in-vitro study JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.04.429852 DO 10.1101/2021.02.04.429852 A1 Hector S. Alvarez-Manzo A1 Yumin Zhang A1 Wanliang Shi A1 Ying Zhang YR 2021 UL http://biorxiv.org/content/early/2021/02/05/2021.02.04.429852.abstract AB Lyme disease (LD) is the most common vector-borne disease in USA and Europe and is caused by Borrelia burgdorferi. Despite proper treatment, approximately one fifth of patients will develop post-treatment LD syndrome (PTLDS), a condition which is poorly understood. One of the possible causes is thought to be due to persister forms of B. burgdorferi that are not effectively killed by the current Lyme antibiotics. In this study, we evaluated nitroxoline, an antibiotic used to treat urinary tract infections, for its activity against a stationary-phase culture enriched with persister forms of B. burgdorferi. Nitroxoline was found to be equivalent in activity against B. burgdorferi to cefuroxime (standard Lyme antibiotic) in different experiments. Moreover, we found that the three-drug combination cefuroxime + nitroxoline + clarithromycin eradicated 98.3% of stationary phase bacteria in the drug-exposure experiment and prevented the regrowth in the subculture study after drug exposure, as well as two-drug combinations cefuroxime + nitroxoline and clarithromycin + nitroxoline. These drug combinations should be further evaluated in a LD mouse model to assess if eradication of persister forms of B. burgdorferi in-vivo is possible and if so, whether nitroxoline could be repurposed as an alternative drug for the treatment of LD.Competing Interest StatementThe authors have declared no competing interest.