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A drug-free strategy to combat bacterial infections with magnetic nanoparticles biosynthesized in bacterial pathogens
Swati Kaushik1, Jijo Thomas1, Vineeta Panwar1
1Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector 81, Mohali, Punjab 140306, India. deepa.ghosh@inst.ac.in.
Abstract:
The extensive and indiscriminate use of antibiotics in the ongoing COVID-19 pandemic might significantly contribute to the growing number of multiple drug resistant (MDR) bacteria. With the dwindling pipeline of new and effective antibiotics, we might soon end up in a post-antibiotic era, in which even common bacterial infections would be a challenge to control. To prevent this, an antibiotic-free strategy would be highly desirable. Magnetic nanoparticle (MNP)-mediated hyperthermia-induced antimicrobial therapy is an attractive option as it is considered safe for human use. Given that iron and zinc are critical for bacterial virulence, we evaluated the response of multiple pathogenic bacteria to these elements. Treatment with 1 mM iron and zinc precursors resulted in the intracellular biosynthesis of MNPs in multiple Gram-positive and Gram-negative disease-causing bacteria. The superparamagnetic nanoparticles in the treated bacteria/biofilms, generated heat upon exposure to an alternating magnetic field (AMF), which resulted in an increase in the temperature (5-6 °C) of the milieu with a subsequent decrease in bacterial viability. Furthermore, we observed for the first time that virulent bacteria derived from infected samples harbour MNPs, suggesting that the bacteria had biosynthesised the MNPs using the metal ions acquired from the host. AMF treatment of the bacterial isolates from the infected specimens resulted in a strong reduction in viability (3-4 logs) as compared to vancomycin/ciprofloxacin treatment. The therapeutic efficacy of the MNPs to induce bacterial death with AMF alone was confirmed ex vivo using infected tissues. Our proposed antibiotic-free approach for killing bacteria using intracellular MNPs is likely to evolve as a promising strategy to combat a wide range of bacterial infections.
Insights
This study introduces an antibiotic-free method using magnetic nanoparticles (MNPs) to combat drug-resistant bacteria. Intracellular MNPs, generated by bacteria, kill them via heat when exposed to an alternating magnetic field (AMF).
Area of Science:
- Biotechnology
- Microbiology
- Materials Science
Background:
- The rise of multiple drug-resistant (MDR) bacteria poses a significant threat, potentially leading to a post-antibiotic era.
- The limited development of new antibiotics necessitates novel, antibiotic-free therapeutic strategies.
- Iron and zinc are essential for bacterial virulence, making them targets for antimicrobial intervention.
Purpose of the Study:
- To investigate the potential of intracellular magnetic nanoparticle (MNP) biosynthesis in pathogenic bacteria as an antibiotic-free antimicrobial strategy.
- To evaluate the efficacy of MNP-mediated hyperthermia induced by an alternating magnetic field (AMF) against drug-resistant bacteria.
- To explore the natural occurrence of MNPs in bacteria isolated from infected hosts.
Main Methods:
- Pathogenic bacteria were treated with iron and zinc precursors to induce intracellular MNP biosynthesis.
- Treated bacteria and biofilms were exposed to an alternating magnetic field (AMF) to induce hyperthermia.
- Bacterial viability was assessed post-AMF exposure, comparing results with conventional antibiotic treatments.
- Therapeutic efficacy was confirmed ex vivo using infected tissues.
Main Results:
- Intracellular MNPs were successfully synthesized in various Gram-positive and Gram-negative bacteria using iron and zinc precursors.
- AMF exposure led to a temperature increase (5-6 °C) and significant reduction in bacterial viability.
- Virulent bacteria isolated from infected samples were found to harbor MNPs, indicating host-derived metal ion utilization.
- AMF treatment of MNP-containing bacteria demonstrated superior efficacy (3-4 log reduction) compared to vancomycin and ciprofloxacin.
Conclusions:
- Intracellular MNP biosynthesis offers a promising avenue for developing antibiotic-free antimicrobial therapies.
- MNP-mediated hyperthermia presents a safe and effective strategy for combating a broad spectrum of bacterial infections.
- The findings suggest a potential mechanism for bacterial adaptation and survival using host-derived metals, which can be therapeutically exploited.
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