Document Type

Article

Publication Date

2024

Publication Title

Microbiology Spectrum

Volume

12

Issue

1

Pages

e02992-23 (1-17)

DOI

10.1128/spectrum.02992-23

Abstract

Staphylococcus aureus is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant S. aureus (MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this hypothesis, we used three antibiotics approved to treat SSTI, daptomycin, doxycycline, and vancomycin, and compared the cytotoxic effects of these antibiotics administered either before or after nsPEF. Co-treatment with nsPEF and daptomycin greatly potentiated the effects of each monotherapy regardless of their order. Conversely, the sensitivity of MRSA to both doxycycline and vancomycin was increased only when nsPEF preceded the antibiotic incubation. Finally, MRSA cells grown in biofilms were efficiently killed by co-treatment with nsPEF/vancomycin, suggesting that their mutual enhancement is maintained even when treating sessile communities known for their inherent antimicrobial resistance. Altogether our results show that MRSA perturbation by nsPEF potentiates the effect of multiple antibiotics and that the order of the combined treatment can have a major impact on efficacy. Since SSTIs are accessible for physical interventions such as nsPEF stimulus, combinatorial treatments could be used to increase the efficacy of antibiotics used to treat such infections.

Rights

© 2024 Chittams-Miles et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Original Publication Citation

Chittams-Miles Alexandra, E., Malik, A., Purcell Erin, B., & Muratori, C. (2024). Nanosecond pulsed electric fields increase antibiotic susceptibility in methicillin-resistant Staphylococcus aureus. Microbiology Spectrum, 12(1), 1-17, Article e02992-23. https://doi.org/10.1128/spectrum.02992-23

ORCID

0000-0002-8736-0433 (Purcell), 0000-0002-3359-164X (Muratori)

Additional Files
Muratori-2023-NanosecondPulsedSupplementaryMaterial.pdf (546 kB)
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Muratori-2023-NanosecondPulsedElectricFieldsPeerReview.pdf (293 kB)
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