Mild magnetic hyperthermia is synergistic with an antibiotic treatment against dual species biofilms consisting of S. aureus and P. aeruginosa by enhancing metabolic activity

Abstract

Objective

The wound biofilm infections that develop tolerance to standard-of-care antimicrobial treatment has been increasing. The objective of this study was to demonstrate a proof-of-concept of mild magnetic nanoparticle (MNP)/alternating magnetic field (AMF) hyperthermia as an anti-biofilm therapy against multispecies biofilm infections.

Methods

Using both an in vitro cell culture and in vivo murine model of wound infection, we investigated whether MNP/AMF hyperthermia applied at a mild thermal dosage would be synergistically effective against dual species biofilm infection consisting of S. aureus and P. aeruginosa when combined with a broad-spectrum antibiotic, ciprofloxacin (CIP).

Results

The combined treatment of MNP/AMF hyperthermia and CIP to the wounds of diabetic mice (db/db mice) significantly reduced the CFU number of S. aureus and P. aeruginosa by 2-log and 3-log, respectively, compared to the untreated control group, whereas either mild MNP/AMF hyperthermia or CIP treatment alone had little effect on the eradication of both bacteria. Our gene microarray data obtained from the culture of S. aureus biofilm suggest that mild MNP/AMF could shift the expression of genes for cellular respiration from anaerobic fermentation to an aerobic glycolytic/tricarboxylic acid cycle (TCA) pathway, implicating that the beneficial effect of mild MNP/AMF hyperthermia on the increased susceptibility of biofilm bacteria to an antibiotic treatment is associated with an increased metabolic activity.

Conclusion

Our results support the translational potential of mild MNP/AMF as an adjunctive therapy that can be combined with a broad-spectrum antibiotic treatment for the management of wound biofilm infections associated with multispecies bacteria.

Keywords:

• Magnetic nanoparticle hyperthermia
• antibiotics
• dual species biofilm
• S. aureus
• P. aeruginosa

Author contributions

MK conducted the conception and design of the research. LA and MK wrote the first draft of the manuscript. LA, BY, ED, and AO contributed to the acquisition of data. LA, BY, and MK carried out the analysis and interpretation of data. All authors read and approved the final version of the manuscript.

Acknowledgments

The authors thank Dr. Min Gao and Dr. Lu Zou (Advanced Materials and Liquid Crystal Institute at Kent State University, Kent, Ohio) for training and assistance with SEM. This publication was made possible in part by support from the Kent State University Open Access Publishing Fund.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author (MK) upon reasonable request.

Additional information

Funding

This research was supported by the National Institute of Health under R01 NR015674 (to MK).