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Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae.
Sci Rep. 2020 Mar 27; 10(1):5602.SR

Abstract

Neisseria gonorrhoeae represents an urgent public health threat due to the rapid emergence of resistance to current antibiotics and the limited number of anti-gonococcal agents currently in clinical trials. This study utilized a drug repositioning strategy to investigate FDA-approved gold-containing drugs against N. gonorrhoeae. Auranofin, sodium aurothiomalate and aurothioglucose inhibited 48 clinical isolates of N. gonorrhoeae including multidrug-resistant strains at a concentration as low as 0.03 µg/mL. A time-kill assay revealed that auranofin exhibited rapid bactericidal activity against N. gonorrhoeae. Moreover, both sodium aurothiomalate and aurothioglucose did not inhibit growth of vaginal protective commensal lactobacilli. Auranofin, in combination with azithromycin, ceftriaxone, cefixime or tetracycline showed an additive effect against four N. gonorrhoeae strains, suggesting the possibility of using auranofin in dual therapy. Moreover, auranofin reduced the burden of intracellular N. gonorrhoeae by over 99% outperforming the drug of choice ceftriaxone. Auranofin was found superior to ceftriaxone in reducing the secretion of the pro-inflammatory cytokine IL-8 by endocervical cells infected with N. gonorrhoeae. Furthermore, auranofin exhibited a prolonged post-antibiotic effect over 10 h, as well as inability to generate resistant mutants. Overall, the current study suggests that repurposing gold-containing drugs, like auranofin, for treatment of gonorrhea warrants further investigation.

Authors+Show Affiliations

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA.Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, 47907, USA. mseleem@purdue.edu. Purdue Institute of Inflammation, Immunology, and Infectious Disease, West Lafayette, IN, 47907, USA. mseleem@purdue.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32221472

Citation

Elkashif, Ahmed, and Mohamed N. Seleem. "Investigation of Auranofin and Gold-containing Analogues Antibacterial Activity Against Multidrug-resistant Neisseria Gonorrhoeae." Scientific Reports, vol. 10, no. 1, 2020, p. 5602.
Elkashif A, Seleem MN. Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae. Sci Rep. 2020;10(1):5602.
Elkashif, A., & Seleem, M. N. (2020). Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae. Scientific Reports, 10(1), 5602. https://doi.org/10.1038/s41598-020-62696-3
Elkashif A, Seleem MN. Investigation of Auranofin and Gold-containing Analogues Antibacterial Activity Against Multidrug-resistant Neisseria Gonorrhoeae. Sci Rep. 2020 Mar 27;10(1):5602. PubMed PMID: 32221472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae. AU - Elkashif,Ahmed, AU - Seleem,Mohamed N, Y1 - 2020/03/27/ PY - 2019/11/11/received PY - 2020/02/20/accepted PY - 2020/3/30/entrez PY - 2020/3/30/pubmed PY - 2020/3/30/medline SP - 5602 EP - 5602 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Neisseria gonorrhoeae represents an urgent public health threat due to the rapid emergence of resistance to current antibiotics and the limited number of anti-gonococcal agents currently in clinical trials. This study utilized a drug repositioning strategy to investigate FDA-approved gold-containing drugs against N. gonorrhoeae. Auranofin, sodium aurothiomalate and aurothioglucose inhibited 48 clinical isolates of N. gonorrhoeae including multidrug-resistant strains at a concentration as low as 0.03 µg/mL. A time-kill assay revealed that auranofin exhibited rapid bactericidal activity against N. gonorrhoeae. Moreover, both sodium aurothiomalate and aurothioglucose did not inhibit growth of vaginal protective commensal lactobacilli. Auranofin, in combination with azithromycin, ceftriaxone, cefixime or tetracycline showed an additive effect against four N. gonorrhoeae strains, suggesting the possibility of using auranofin in dual therapy. Moreover, auranofin reduced the burden of intracellular N. gonorrhoeae by over 99% outperforming the drug of choice ceftriaxone. Auranofin was found superior to ceftriaxone in reducing the secretion of the pro-inflammatory cytokine IL-8 by endocervical cells infected with N. gonorrhoeae. Furthermore, auranofin exhibited a prolonged post-antibiotic effect over 10 h, as well as inability to generate resistant mutants. Overall, the current study suggests that repurposing gold-containing drugs, like auranofin, for treatment of gonorrhea warrants further investigation. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/32221472/Investigation_of_auranofin_and_gold-containing_analogues_antibacterial_activity_against_multidrug-resistant_Neisseria_gonorrhoeae L2 - http://dx.doi.org/10.1038/s41598-020-62696-3 DB - PRIME DP - Unbound Medicine ER -
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