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

Autor:	Mitini-Nkhoma SC; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Chimbayo ET; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Mzinza DT; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Mhango DV; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Chirambo AP; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Mandalasi C; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Lakudzala AE; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Tembo DL; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi., Jambo KC; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom., Mwandumba HC; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Jun 24; Vol. 12, pp. 665785. Date of Electronic Publication: 2021 Jun 24 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.665785
Abstrakt:	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. Competing Interests: The authors declare that the manuscript was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Mitini-Nkhoma, Chimbayo, Mzinza, Mhango, Chirambo, Mandalasi, Lakudzala, Tembo, Jambo and Mwandumba.)
Databáze:	MEDLINE
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