Cationic antimicrobial peptides and biogenic silver nanoparticles kill mycobacteria without eliciting DNA damage and

Soumitra Mohanty1, Prajna Jena, Ranjit Mehta

  • 1School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India.

Insights

Biogenic silver nanoparticles combined with antimicrobial peptides show promise for treating drug-resistant mycobacteria. This combination enhances killing effects against Mycobacterium smegmatis and Mycobacterium marinum, offering a new therapeutic strategy.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Microbiology

Background:

  • Multidrug-resistant mycobacteria necessitate novel therapeutic approaches.
  • Antimicrobial peptides (AMPs) and silver nanoparticles (AgNPs) show antibacterial potential but require further evaluation against mycobacteria.
  • Biogenic synthesis of AgNPs offers a sustainable method for nanoparticle production.

Purpose of the Study:

  • To synthesize biogenic AgNPs using various biomasses.
  • To evaluate the antimycobacterial activity of AgNPs alone and in combination with AMPs against Mycobacterium smegmatis and Mycobacterium marinum.
  • To assess the safety and cellular interactions of AgNPs with macrophages.

Main Methods:

  • Synthesis of AgNPs using bacterial, fungal, and plant biomass.
  • Antimicrobial susceptibility testing of AgNPs and AMPs against M. smegmatis and M. marinum.
  • Characterization of AgNPs using transmission electron microscopy and dynamic light scattering.
  • Cytotoxicity assays, DNA damage assessment, and apoptosis studies on macrophages.
  • Intracellular killing assays using fluorescein isothiocyanate-labeled AgNPs.

Main Results:

  • Biogenic AgNPs demonstrated varying susceptibility against M. smegmatis and M. marinum.
  • Specific AMPs (NK-2, LLKKK-18) showed enhanced antimycobacterial activity when combined with certain AgNPs (NP-1, NP-2) at 0.5 ppm.
  • AgNPs combined with rifampin increased the killing of M. smegmatis.
  • AgNPs exhibited no cytotoxicity or DNA damage at mycobactericidal doses but showed toxicity at higher concentrations.
  • Macrophages actively internalized AgNPs, leading to nitric oxide-independent intracellular killing of M. smegmatis.
  • Higher AgNP doses induced G1-phase arrest in macrophages.

Conclusions:

  • Biogenic AgNPs combined with AMPs represent a promising strategy against mycobacterial infections.
  • The synergistic effects observed suggest potential for developing novel antimycobacterial therapies.
  • AgNPs demonstrate a favorable safety profile at therapeutic concentrations, with macrophages playing a key role in intracellular pathogen clearance.

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