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Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions
Neisseria gonorrhoeae has developed resistance to all previous antibiotics used for treatment. This highlights a crucial need for novel antimicrobials to treat gonococcal infections. We previously showed that carbamazepine (Cz), one of the most commonly prescribed antiepileptic drugs, can block the...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872610/ https://www.ncbi.nlm.nih.gov/pubmed/36602335 http://dx.doi.org/10.1128/aac.00968-22 |
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author | Shewell, Lucy K. Day, Christopher J. De Bisscop, Xavier Edwards, Jennifer L. Jennings, Michael P. |
author_facet | Shewell, Lucy K. Day, Christopher J. De Bisscop, Xavier Edwards, Jennifer L. Jennings, Michael P. |
author_sort | Shewell, Lucy K. |
collection | PubMed |
description | Neisseria gonorrhoeae has developed resistance to all previous antibiotics used for treatment. This highlights a crucial need for novel antimicrobials to treat gonococcal infections. We previously showed that carbamazepine (Cz), one of the most commonly prescribed antiepileptic drugs, can block the interaction between gonococcal pili and the I-domain region of human complement receptor 3 (CR3)—an interaction that is vital for infection of the female cervix. We also show that Cz can completely clear an established N. gonorrhoeae infection of primary human cervical cells. In this study, we quantified Cz in serum, saliva, and vaginal fluid collected from 16 women who were, or were not, regularly taking Cz. We detected Cz in lower reproductive tract mucosal secretions in the test group (women taking Cz) at potentially therapeutic levels using a competitive ELISA. Furthermore, we found that Cz concentrations present in vaginal fluid from women taking this drug were sufficient to result in a greater than 99% reduction (within 24 h) in the number of viable gonococci recovered from ex vivo, human, primary cervical cell infections. These data provide strong support for the further development of Cz as a novel, host-targeted therapy to treat gonococcal cervicitis. |
format | Online Article Text |
id | pubmed-9872610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-98726102023-01-25 Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions Shewell, Lucy K. Day, Christopher J. De Bisscop, Xavier Edwards, Jennifer L. Jennings, Michael P. Antimicrob Agents Chemother Experimental Therapeutics Neisseria gonorrhoeae has developed resistance to all previous antibiotics used for treatment. This highlights a crucial need for novel antimicrobials to treat gonococcal infections. We previously showed that carbamazepine (Cz), one of the most commonly prescribed antiepileptic drugs, can block the interaction between gonococcal pili and the I-domain region of human complement receptor 3 (CR3)—an interaction that is vital for infection of the female cervix. We also show that Cz can completely clear an established N. gonorrhoeae infection of primary human cervical cells. In this study, we quantified Cz in serum, saliva, and vaginal fluid collected from 16 women who were, or were not, regularly taking Cz. We detected Cz in lower reproductive tract mucosal secretions in the test group (women taking Cz) at potentially therapeutic levels using a competitive ELISA. Furthermore, we found that Cz concentrations present in vaginal fluid from women taking this drug were sufficient to result in a greater than 99% reduction (within 24 h) in the number of viable gonococci recovered from ex vivo, human, primary cervical cell infections. These data provide strong support for the further development of Cz as a novel, host-targeted therapy to treat gonococcal cervicitis. American Society for Microbiology 2023-01-05 /pmc/articles/PMC9872610/ /pubmed/36602335 http://dx.doi.org/10.1128/aac.00968-22 Text en Copyright © 2023 Shewell et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Experimental Therapeutics Shewell, Lucy K. Day, Christopher J. De Bisscop, Xavier Edwards, Jennifer L. Jennings, Michael P. Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions |
title | Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions |
title_full | Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions |
title_fullStr | Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions |
title_full_unstemmed | Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions |
title_short | Repurposing Carbamazepine To Treat Gonococcal Infection in Women: Oral Delivery for Control of Epilepsy Generates Therapeutically Effective Levels in Vaginal Secretions |
title_sort | repurposing carbamazepine to treat gonococcal infection in women: oral delivery for control of epilepsy generates therapeutically effective levels in vaginal secretions |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872610/ https://www.ncbi.nlm.nih.gov/pubmed/36602335 http://dx.doi.org/10.1128/aac.00968-22 |
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