Screening of FDA-approved drugs using a 384-wellplate-based biofilm platform: the case of fingolimod

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Gilbert-Girard , S , Savijoki , K , Yli-Kauhaluoma , J & Fallarero , A 2020 , ' Screening of FDA-approved drugs using a 384-wellplate-based biofilm platform: the case of fingolimod ' , Microorganisms , vol. 8 , no. 11 , 1834 . https://doi.org/10.3390/microorganisms8111834

Title: Screening of FDA-approved drugs using a 384-wellplate-based biofilm platform: the case of fingolimod
Author: Gilbert-Girard, Shella; Savijoki, Kirsi; Yli-Kauhaluoma, Jari; Fallarero, Adyary
Other contributor: University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Pharmaceutical Design and Discovery group
University of Helsinki, Divisions of Faculty of Pharmacy







Date: 2020-11-21
Language: eng
Number of pages: 25
Belongs to series: Microorganisms
ISSN: 2076-2607
DOI: https://doi.org/10.3390/microorganisms8111834
URI: http://hdl.handle.net/10138/322866
Abstract: In an effort to find new repurposed antibacterial compounds, we performed the screening of an FDA-approved compounds library against Staphylococcus aureus American Type Culture Collection (ATCC) 25923. Compounds were evaluated for their capacity to prevent both planktonic growth and biofilm formation as well as to disrupt pre-formed biofilms. One of the identified initial hits was fingolimod (FTY720), an immunomodulator approved for the treatment of multiple sclerosis, which was then selected for follow-up studies. Fingolimod displayed a potent activity against S. aureus and S. epidermidis with a minimum inhibitory concentration (MIC) within the range of 12-15 mu M at which concentration killing of all the bacteria was confirmed. A time-kill kinetic study revealed that fingolimod started to drastically reduce the viable bacterial count within two hours and we showed that no resistance developed against this compound for up to 20 days. Fingolimod also displayed a high activity against Acinetobacter baumannii (MIC 25 mu M) as well as a modest activity against Escherichia coli and Pseudomonas aeruginosa. In addition, fingolimod inhibited quorum sensing in Chromobacterium violaceum and might therefore target this signaling pathway in certain Gram-negative bacteria. In conclusion, we present the identification of fingolimod from a compound library and its evaluation as a potential repurposed antibacterial compound.
Subject: 317 Pharmacy
fingolimod
biofilm
antibacterial
screening
quorum sensing
Staphylococcus aureus
Acinetobacter baumannii
Pseudomonas aeruginosa
INFECTIOUS-DISEASES-SOCIETY
STAPHYLOCOCCUS-AUREUS
SPHINGOID BASES
SPHINGOLIPIDS
SUSCEPTIBILITY
MECHANISMS
RESISTANCE
TOLERANCE
DISCOVERY
DESIGN
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