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. 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.665785

DOI=10.3389/fimmu.2021.665785

ISSN=1664-3224

ABSTRACT=Tuberculosis (TB) remains a challenging global health concern and claims more lives than any other infectious disease 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. A faster and cheaper alternative is to repurpose existing drugs for TB treatment. There is growing interest in the use of immunomodulators 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.