Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection - PubMed (original) (raw)
Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection
Jie Feng et al. Emerg Microbes Infect. 2015.
Abstract
Lyme disease is the leading tick-borne disease in the USA. Whereas the majority of Lyme disease patients with early disease can be cured with standard treatment, some patients suffer from chronic fatigue and joint and muscular pain despite treatment, a syndrome called posttreatment Lyme disease syndrome. Although the cause is unclear, ineffective killing of Borrelia burgdorferi persisters by current Lyme disease antibiotics is one possible explanation. We took advantage of our recently developed high-throughput viability assay and screened the National Cancer Institute compound library collection consisting of 2526 compounds against stationary phase B. burgdorferi. We identified the top 30 new active hits, including the top six anthracycline antibiotics daunomycin 3-oxime, dimethyldaunomycin, daunomycin, NSC299187, NSC363998 and nogalamycin, along with other compounds, including prodigiosin, mitomycin, nanaomycin and dactinomycin, as having excellent activity against B. burgdorferi stationary phase culture. The anthracycline or anthraquinone compounds, which are known to have both anti-cancer and antibacterial activities, also had high activity against growing B. burgdorferi with low minimum inhibitory concentration. Future studies on the structure-activity relationship and mechanisms of action of anthracyclines/anthraquinones are warranted. In addition, drug combination studies with the anthracycline class of compounds and the current Lyme antibiotics to eradicate B. burgdorferi persisters in vitro and in animal models are needed to determine if they improve the treatment of Lyme disease.
Figures
Figure 1
Representative images at ×100 magnification of stationary phase B. burgdorferi treated with different compounds (50 μM) followed by staining with the SYBR Green I/PI assay. Abbreviations: DOX, doxycycline; AMO, amoxicillin; DAP, daptomycin; DAU, daunomycin; NOG, nogalamycin; PYR, pyrromycin; RHO, Rhodomycin A; CHA, chaetochromin; PRO, prodigiosin; MIT, mitomycin; NAN, nanaomycin; DAC, dactinomycin; EMO, emodin.
Figure 2
Representative images at ×100 magnification of stationary phase B. burgdorferi strain B31 treated with different compounds (20 μM) followed by staining with the SYBR Green I/PI assay. Abbreviations: DOX, doxycycline; DAP, daptomycin; DAU, daunomycin; NOG, nogalamycin; PYR, pyrromycin; RHO, Rhodomycin A; CHA, chaetochromin; PRO, prodigiosin; NAN, nanaomycin.
Similar articles
- Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening.
Pothineni VR, Wagh D, Babar MM, Inayathullah M, Solow-Cordero D, Kim KM, Samineni AV, Parekh MB, Tayebi L, Rajadas J. Pothineni VR, et al. Drug Des Devel Ther. 2016 Apr 1;10:1307-22. doi: 10.2147/DDDT.S101486. eCollection 2016. Drug Des Devel Ther. 2016. PMID: 27103785 Free PMC article. - Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells.
Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Sharma B, et al. Antimicrob Agents Chemother. 2015 Aug;59(8):4616-24. doi: 10.1128/AAC.00864-15. Epub 2015 May 26. Antimicrob Agents Chemother. 2015. PMID: 26014929 Free PMC article. - Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library.
Feng J, Wang T, Shi W, Zhang S, Sullivan D, Auwaerter PG, Zhang Y. Feng J, et al. Emerg Microbes Infect. 2014 Jul;3(7):e49. doi: 10.1038/emi.2014.53. Epub 2014 Jul 2. Emerg Microbes Infect. 2014. PMID: 26038747 Free PMC article. - Standardised in vitro susceptibility testing of Borrelia burgdorferi against well-known and newly developed antimicrobial agents--possible implications for new therapeutic approaches to Lyme disease.
Hunfeld KP, Kraiczy P, Kekoukh E, Schäfer V, Brade V. Hunfeld KP, et al. Int J Med Microbiol. 2002 Jun;291 Suppl 33:125-37. doi: 10.1016/s1438-4221(02)80024-8. Int J Med Microbiol. 2002. PMID: 12141737 Review. - Borrelia burgdorferi glycosaminoglycan-binding proteins: a potential target for new therapeutics against Lyme disease.
Lin YP, Li L, Zhang F, Linhardt RJ. Lin YP, et al. Microbiology (Reading). 2017 Dec;163(12):1759-1766. doi: 10.1099/mic.0.000571. Epub 2017 Nov 8. Microbiology (Reading). 2017. PMID: 29116038 Free PMC article. Review.
Cited by
- Rapid determination of antibiotic susceptibility of clinical isolates of Escherichia coli by SYBR green I/Propidium iodide assay.
Cui X, Liu S, Jin Y, Li M, Shao C, Yu H, Zhang Y, Liu Y, Wang Y. Cui X, et al. Sci Rep. 2024 Aug 13;14(1):18782. doi: 10.1038/s41598-024-69286-7. Sci Rep. 2024. PMID: 39138327 Free PMC article. - Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease.
Alruwaili Y, Jacobs MB, Hasenkampf NR, Tardo AC, McDaniel CE, Embers ME. Alruwaili Y, et al. Front Microbiol. 2023 Nov 21;14:1293300. doi: 10.3389/fmicb.2023.1293300. eCollection 2023. Front Microbiol. 2023. PMID: 38075920 Free PMC article. - Concurrent Infection of the Human Brain with Multiple Borrelia Species.
Golovchenko M, Opelka J, Vancova M, Sehadova H, Kralikova V, Dobias M, Raska M, Krupka M, Sloupenska K, Rudenko N. Golovchenko M, et al. Int J Mol Sci. 2023 Nov 29;24(23):16906. doi: 10.3390/ijms242316906. Int J Mol Sci. 2023. PMID: 38069228 Free PMC article. - Lyme disease and the pursuit of a clinical cure.
Adkison H, Embers ME. Adkison H, et al. Front Med (Lausanne). 2023 May 24;10:1183344. doi: 10.3389/fmed.2023.1183344. eCollection 2023. Front Med (Lausanne). 2023. PMID: 37293310 Free PMC article. Review. - Upcycling the anthracyclines: New mechanisms of action, toxicology, and pharmacology.
Bayles CE, Hale DE, Konieczny A, Anderson VD, Richardson CR, Brown KV, Nguyen JT, Hecht J, Schwartz N, Kharel MK, Amissah F, Dowling TC, Nybo SE. Bayles CE, et al. Toxicol Appl Pharmacol. 2023 Jan 15;459:116362. doi: 10.1016/j.taap.2022.116362. Epub 2022 Dec 30. Toxicol Appl Pharmacol. 2023. PMID: 36592899 Free PMC article. Review.
References
- Centers for Disease Control and Prevention. Lyme Disease. Atlanta: CDC, 2014. Available at: http://www.cdc.gov/lyme/(accessed 13 September 2014) .
- Centers for Disease Control and Prevention. Post-treatment Lyme Disease Syndrome. Atlanta: CDC, 2014. Available at : http://www.cdc.gov/lyme/postLDS/index.html (accessed 13 September 2014).
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical