{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:44:36Z","timestamp":1785912276370,"version":"3.56.0"},"reference-count":220,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["ADVANCE\u2010TB CA21164"],"award-info":[{"award-number":["ADVANCE\u2010TB CA21164"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The global burden of multidrug\u2010resistant tuberculosis (MDR\u2010TB) and the rising incidence of nontuberculous mycobacterial (NTM) infections highlight the urgent need for innovative therapeutic strategies. Current treatments are prolonged, toxic, and increasingly compromised by resistance and limited diagnostic capacity. This review focuses on emerging therapeutic strategies against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) and highlights evidence relevant to NTM whenever available. Specifically, it explores direct anti\u2010mycobacterial small molecules, including the optimization of drug classes, such as hydrazide\u2010hydrazones, isoniazid derivatives, nitrofurans, multicomponent forms, and metal complexes, as well as emerging chemical entities in early\u2010stage development. These compounds target essential bacterial enzymes such as decaprenylphosphoryl\u2010\u03b2\u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010ribose oxidase (DprE1), enoyl acyl carrier protein reductase (InhA), and deoxyribonucleic acid (DNA) gyrase inhibitors, offering promising avenues for overcoming resistance. The review also examines natural products and phytochemicals, including siderophore inhibitors, plant\u2010derived compounds, and essential oils. Non\u2010classical strategies such as antimicrobial peptides (AMPs) and phage therapy are also discussed. Finally, we discuss the expanding field of host\u2010directed therapies (HDTs), which aim to modulate the host immune response to enhance mycobacterial clearance and reduce tissue damage. Ultimately, advancing mycobacterial treatment will require integrated, mechanism\u2010based regimens that combine new compounds with HDTs and improved delivery systems. Although therapeutic innovation for NTM has lagged, adapting promising TB\u2010focused compounds and implementing NTM\u2010specific screening and validation frameworks are essential. Collaborative efforts across academia, industry, and the public health sector will be key to translating these advances into shorter, safer, and more effective therapies that address the complexity of mycobacterial disease and the rise of antimicrobial resistance.\n                  <\/jats:p>","DOI":"10.1002\/med.70096","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:49:01Z","timestamp":1785908941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advancing Therapies for Mycobacterial Diseases: From Small Molecules to Host\u2010Directed Strategies"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-1487","authenticated-orcid":false,"given":"T\u00e2nia","family":"Silva","sequence":"first","affiliation":[{"name":"i3S \u2010 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto Porto Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Aiello","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases L. 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