An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA)
Abstract
:1. Introduction
2. Results and Discussion
Drugs Found in This Screen | Original Indication | Administration Route | Keratinocyte GI50 (μM) | MRSA MICs (μM) | |||
---|---|---|---|---|---|---|---|
USA 100 | USA 300 | USA 400 | VISA | ||||
Ivacaftor | cystic fibrosis | OR | 5.9 ± 0.5 | 6.25 | 6.25 | 6.25 | 6.25 |
5-fluorouracil | cancer | IV, TO | 33.3 ± 2.6 | 6.25 | 3.13 | 3.13 | 6.25 |
Penfluridol | psychosis | OR | 2.1 ± 0.6 | 3.13 | 3.13 | 3.13 | 3.13 |
Niclosamide | anthelmintic | OR | <0.2 | 0.78 | 0.39 | 0.78 | 0.39 |
Gemcitabine | cancer | IV | 1.9 ± 0.2 | 0.10 | 0.05 | 0.10 | 0.05 |
Floxuridine | cancer | IV | >50 | 0.025 | 0.00313 | 0.0125 | 0.00625 |
FDA-approved MRSA drugs | |||||||
Clindamycin | MRSA infection | IV, OR, TO | >50 | >100 | 0.20 | 0.20 | >100 |
Doxycycline | MRSA infection | IV, OR | 36.9 ± 3.7 | 0.39 | 0.78 | 1.56 | 12.5 |
Linezolid | MRSA infection | IV, OR | >100 | 6.25 | 6.25 | 6.25 | 3.13 |
Mupirocin | MRSA infection | TO | >50 | 0.78 | 0.39 | 0.39 | >100 |
Tigecycline | MRSA infection | IV | 20.6 ± 4.2 | 0.78 | 0.78 | 0.78 | 1.56 |
Vancomycin | MRSA infection | IV | >100 | 0.78 | 0.78 | 0.78 | 6.25 |
2.1. Ivacaftor
2.2. 5-Flurouracil
2.3. Penfluridol
2.4. Niclosamide
2.5. Gemcitabine
2.6. Floxuridine
3. Experimental Section
3.1. Compound Library, Test Compounds and Bacteria
3.2. Single-Point Bacteria Growth Inhibition Assay
3.3. Minimum Inhibitory Concentration (MIC) Assay
3.4. Human Epidermal Keratinocyte Viability (GI50) Assay
3.5. Bactericidal/Static Determination Assay
3.6. Time-Kill Assay
4. Conclusions
Supplementary Files
Supplementary File 1Acknowledgments
Author Contributions
Conflicts of Interests
References
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Lau, Q.Y.; Tan, Y.Y.F.; Goh, V.C.Y.; Lee, D.J.Q.; Ng, F.M.; Ong, E.H.Q.; Hill, J.; Chia, C.S.B. An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA). Antibiotics 2015, 4, 424-434. https://doi.org/10.3390/antibiotics4040424
Lau QY, Tan YYF, Goh VCY, Lee DJQ, Ng FM, Ong EHQ, Hill J, Chia CSB. An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA). Antibiotics. 2015; 4(4):424-434. https://doi.org/10.3390/antibiotics4040424
Chicago/Turabian StyleLau, Qiu Ying, Yoke Yan Fion Tan, Vanessa Chai Yin Goh, David Jing Qin Lee, Fui Mee Ng, Esther H. Q. Ong, Jeffrey Hill, and Cheng San Brian Chia. 2015. "An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA)" Antibiotics 4, no. 4: 424-434. https://doi.org/10.3390/antibiotics4040424