Magnetic hyperthermia drastically enhances killing of Mycobacterium tuberculosis by bacteriocin AS-48 grafted on biomimetic nanoparticles

Abstract

Mycobacterium tuberculosis, the etiological agent of human tuberculosis, is an intracellular pathogen responsible for one of the infectious diseases with highest mortality rates. Its ability to replicate inside alveolar macrophages and trigger the formation of granulomas, alongside the appearance of multidrug-resistant strains, impose the employment of drugs that exacerbate their toxic effects after the long therapies necessary to deal with the infection. As an alternative to conventional drugs, this work proposes the use of bacteriocin AS-48 immobilized on biomimetic magnetic nanoparticles (BMNPs) as a nanoformulation capable of killing M. tuberculosis in infected THP-1 macrophages, which allows combination with magnetic hyperthermia to increase its effectiveness. This work is a proof of concept of a nanosystem that could potentially be magnetically directed to infected areas, where it could be applied locally. Our results show that AS-48_BMNP nanoassemblies used against M. tuberculosis in vitro display a synergistic effect with magnetic hyperthermia that can completely eradicate the bacteria from infected macrophages in four days. This combined treatment represents a promising opportunity for the future development of a local therapy for the treatment of M. tuberculosis.