Abstract

Tuberculosis (TB) is a leading cause of death from a single infectious agent, Mycobacterium tuberculosis (Mtb). Although progress has been made in TB control, still about 10 million people worldwide develop TB annually and 1.5 million die of the disease. The rapid emergence of aggressive, drug-resistant strains and latent infections have caused TB to remain a global health challenge. TB treatments are lengthy and their side effects lead to poor patient compliance, which in turn has contributed to the drug resistance and exacerbated the TB epidemic. The relatively low output of newly approved antibiotics has spurred research interest toward alternative antibacterial molecules such as silver nanoparticles (AgNPs). In the present study, we use the natural biopolymer alginate to serve as a stabilizer and/or reductant to green synthesize AgNPs, which improves their biocompatibility and avoids the use of toxic chemicals. The average size of the alginate-capped AgNPs (ALG-AgNPs) was characterized as nanoscale, and the particles were round in shape. Drug susceptibility tests showed that these ALG-AgNPs are effective against both drug-resistant Mtb strains and dormant Mtb. A bacterial cell-wall permeability assay showed that the anti-mycobacterial action of ALG-AgNPs is mediated through an increase in cell-wall permeability. Notably, the anti-mycobacterial potential of ALG-AgNPs was effective in both zebrafish and mouse TB animal models in vivo. These results suggest that ALG-AgNPs could provide a new therapeutic option to overcome the difficulties of current TB treatments.

Highlights

  • Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (Mtb) and remains the leading cause of mortality among infectious diseases worldwide

  • Four or five second-line anti-TB drugs are usually employed as part of the regimen to treat multidrug-resistant tuberculosis (MDR-TB) and XDR-TB, these agents target only a small number of cellular processes for inhibition of Mtb, namely protein translation, ATP synthesis, lipid catabolism, and transport, which may give rise to cross-resistance during longterm therapy (Alzahabi et al, 2020)

  • Our previous report showed that polysaccharides can be used as both a reducing agent and a stabilizing agent to prepare AgNPs (Cheng et al, 2014); the reduction reaction progressed very slowly at room temperature

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Summary

Introduction

Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (Mtb) and remains the leading cause of mortality among infectious diseases worldwide. Antimycobacterial Alginate-Capped Silver Nanoparticles (INH) and rifampicin (RIF) is defined as multidrug-resistant tuberculosis (MDR-TB), whereas resistance to INH, RIF, any fluoroquinolone, and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin) is defined as extensively drug-resistant tuberculosis (XDR-TB) (Seung et al, 2015; Prasanna and Niranjan, 2019). Four or five second-line anti-TB drugs are usually employed as part of the regimen to treat MDR-TB and XDR-TB, these agents target only a small number of cellular processes for inhibition of Mtb, namely protein translation, ATP synthesis, lipid catabolism, and transport, which may give rise to cross-resistance during longterm therapy (Alzahabi et al, 2020). The lengthy, complex regimen and toxic side effects can result in partial non-compliance that may cause either treatment failure or the emergence of new drug resistance. There is an unmet need for developing novel therapeutics and improved intervention against TB

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