Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria

Abstract

e Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections. Staphylococcus aureus is a major pathogen that produces toxins and superantigens causing skin and soft tissue infections in hospitals or communities (1-3). Antibiotic therapy is not highly efficient because the routine and intensive use of antibiotics has caused the emergence of both hospital-and community-associated methicillin-resistant S. aureus. Moreover, S. aureus tends to form biofilms that reduce the susceptibility of the pathogen to the immune system and topical antimicrobials, rendering treatment of infections using antibiotics less effective (4). The need to develop alternative therapeutic treatments against S. aureus to address this major public health problem is urgent. Nanomaterials provide attractive options to resolve this problem. Various technologies using nanosized and microsized carriers have been developed to increase the low rate of penetration of active agents through the skin (5, 6). Hyperthermia is a therapeutic procedure that increases tissue temperatures by using physical methods, such as microwave, radiofrequency, laser, and ultrasound. However, a bottleneck for the clinical application of hyperthermia is the difficulty of controlling the temperature temporally and spatially, particularly in deep body regions. Magnetic hyperthermia offers an attractive solution to this problem. Upon exposure to an alternating magnetic field, magnetic nanoparticles (MNPs) produce heat mainly on the basis of the mechanisms of hysteresis losses (7), relaxation losses (Néel or Brown relaxation) (8-10), and eddy current effect (11). Magnetic hyperth...

Accumulation and Dissolution of Magnetite Crystals in a Magnetically Responsive Ciliate

“…With the discovery of MTB-grazing protozoa, we can envision a synthetic magnetization with the cocultivation of MTB with heterotrophic protozoa. This could be very useful for the sequestration of magnetosomes and their concentration into individual eukaryotic cells and might significantly improve some medical applications (e.g., drug delivery) that have been so far developed using cultured MTB (53)(54)(55). Heterotrophic bacteriovorus U. marinum and related species have been cultivated for years and are available in culture collections (36,37).…”

Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents

“…[35,36] However, the number of works on magnetic hyperthermia performance of the "whole" magnetotactic bacteria is very limited. Song et al [37] found that magnetotactic bacteria under an external alternating magnetic field (AMF) can be used to kill Staphylococcus aureus, a common hospital and household pathogen. And Alphandéry et al [26] showed that intact bacterial cells containing chains of magnetosomes exhibit high specific absorption rates (SARs) of 625 W g −1 at 880 Oe and 108 kHz.…”

Steering of magnetotactic bacterial microrobots by focusing magnetic field for targeted pathogen killing

“…Magnetotactic bacteria can be constructed as drug-carrier microrobots [15,16]. Applying an alternating magnetic field to induce magnetic hyperthermia of magnetotactic bacteria is an alternative [22,23]. However, these applications generally needs two sets of independent devices that can generate guiding and alternating magnetic fields respectively.…”