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New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics
Author(s) -
Hawn Thomas R.,
Shah Javeed A.,
Kalman Daniel
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12255
Subject(s) - tuberculosis , antibiotics , disease , pandemic , immune system , mycobacterium tuberculosis , biology , immunology , drug resistance , antibiotic resistance , infectious disease (medical specialty) , medicine , microbiology and biotechnology , covid-19 , pathology
Summary Despite the availability of M ycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis ( TB ) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co‐infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here, we discuss recent progress in so‐called ‘host‐directed therapeutics’ ( HDT s), focusing on two general mechanistic strategies: (i) HDT s that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDT s that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDT s hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic‐resistant strains, and may have activity against non‐replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDT s to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDT s as effective adjunctive treatment options for TB .