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Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents

Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of mult...

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Autores principales: Mitini-Nkhoma, Steven C., Chimbayo, Elizabeth T., Mzinza, David T., Mhango, David V., Chirambo, Aaron P., Mandalasi, Christine, Lakudzala, Agness E., Tembo, Dumizulu L., Jambo, Kondwani C., Mwandumba, Henry C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264357/
https://www.ncbi.nlm.nih.gov/pubmed/34248944
http://dx.doi.org/10.3389/fimmu.2021.665785
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author Mitini-Nkhoma, Steven C.
Chimbayo, Elizabeth T.
Mzinza, David T.
Mhango, David V.
Chirambo, Aaron P.
Mandalasi, Christine
Lakudzala, Agness E.
Tembo, Dumizulu L.
Jambo, Kondwani C.
Mwandumba, Henry C.
author_facet Mitini-Nkhoma, Steven C.
Chimbayo, Elizabeth T.
Mzinza, David T.
Mhango, David V.
Chirambo, Aaron P.
Mandalasi, Christine
Lakudzala, Agness E.
Tembo, Dumizulu L.
Jambo, Kondwani C.
Mwandumba, Henry C.
author_sort Mitini-Nkhoma, Steven C.
collection PubMed
description Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most Mycobacterium tuberculosis (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb’s differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs de-novo is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host’s antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents.
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spelling pubmed-82643572021-07-09 Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents Mitini-Nkhoma, Steven C. Chimbayo, Elizabeth T. Mzinza, David T. Mhango, David V. Chirambo, Aaron P. Mandalasi, Christine Lakudzala, Agness E. Tembo, Dumizulu L. Jambo, Kondwani C. Mwandumba, Henry C. Front Immunol Immunology Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most Mycobacterium tuberculosis (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb’s differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs de-novo is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host’s antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents. Frontiers Media S.A. 2021-06-24 /pmc/articles/PMC8264357/ /pubmed/34248944 http://dx.doi.org/10.3389/fimmu.2021.665785 Text en Copyright © 2021 Mitini-Nkhoma, Chimbayo, Mzinza, Mhango, Chirambo, Mandalasi, Lakudzala, Tembo, Jambo and Mwandumba https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Mitini-Nkhoma, Steven C.
Chimbayo, Elizabeth T.
Mzinza, David T.
Mhango, David V.
Chirambo, Aaron P.
Mandalasi, Christine
Lakudzala, Agness E.
Tembo, Dumizulu L.
Jambo, Kondwani C.
Mwandumba, Henry C.
Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents
title Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents
title_full Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents
title_fullStr Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents
title_full_unstemmed Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents
title_short Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents
title_sort something old, something new: ion channel blockers as potential anti-tuberculosis agents
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264357/
https://www.ncbi.nlm.nih.gov/pubmed/34248944
http://dx.doi.org/10.3389/fimmu.2021.665785
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