Novel strategies based on natural products and synthetic derivatives to overcome resistance in Mycobacterium tuberculosis

One of the biggest health challenges of today's world is the emergence of antimicrobial resistance (AMR), which renders conventional therapeutics insufficient and urgently demands the generation of novel antimicrobial strategies. Mycobacterium tuberculosis (M. tuberculosis), the pathogen causing tuberculosis (TB), is among the most successful bacteria producing drug-resistant infections. The versatility of M. tuberculosis allows it to evade traditional anti-TB agents through various acquired and intrinsic mechanisms, rendering TB among the leading causes of infectious disease-related mortality. In this context, researchers worldwide focused on establishing novel approaches to address drug resistance in M. tuberculosis, developing diverse alternative treatments with varying effectiveness and in different testing phases. Overviewing the current progress, this paper aims to briefly present the mechanisms involved in M. tuberculosis drug-resistance, further reviewing in more detail the under-development antibiotics, nanotechnological approaches, and natural therapeutic solutions that promise to overcome current treatment limitations. [Display omitted] •Resistant TB ranks high among infectious disease deaths.•New antibiotics, repurposed drugs, nanotech, natural therapies are reviewed.•Curcumin, quercetin, phloretin, polyphenols: preclinical promising results.•Nanotech alternatives show promise in vitro/in vivo; no clinical trials completed.•Polymer and lipid-based nanomaterials lead in anti-TB drug delivery research.