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Nanosecond electric pulses rapidly enhance the inactivation of Gram-negative bacteria using Gram-positive antibiotics

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Abstract

Physically disrupting microorganism membranes to enable antibiotics to overcome resistance mechanisms that inhibit or excrete antibiotics has great potential for reducing antibiotic doses and rendering resistance mechanisms inert. We demonstrate the synergistic inactivation of a Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria by combining 222 30 kV/cm electric pulses (EPs) or 500 20 kV/cm EPs with 300-ns EP duration with various antibiotics with different mechanisms of action is demonstrated. Doses of antibiotics that produced no inactivation in 10 min of exposure in solution with bacteria induced several log reductions under the influence of nanosecond EPs. Combining 2 μg/L or 20 μg/mL of rifampicin with the 30 kV/cm EPs enhanced Staphylococcus aureus inactivation compared with EPs alone, while only a few of the other combinations demonstrated improvement. Combining 2 μg/L or 20 μg/mL of mupirocin or rifampicin with either EP train enhanced E. coli inactivation compared with EPs alone. Combining 2 μg/L or 20 μg/mL of erythromycin or vancomycin with the 30 kV/cm EPs enhanced E. coli inactivation compared with EPs alone. These results indicate that EPs can make Gram-positive antibiotics efficient for inactivating Gram-negative bacteria with future studies required to optimize EP parameters for other antibiotics and Gram-negative bacteria.

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Acknowledgments

We thank Alan Kraft for his assistance with performing temperature measurements across the cuvettes during electric pulse applications.

Funding

This work was funded by a Purdue Research Foundation Doctoral Fellowship. We thank Nanovis, LLC, for providing materials.

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Author notes

  1. Ram Anand Vadlamani and Agni Dhanabal contributed equally to this work.

Authors and Affiliations

  1. School of Nuclear Engineering, Purdue University, West Lafayette, IN, USA

    Ram Anand Vadlamani & Allen L. Garner

  2. Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN, USA

    Agni Dhanabal & Allen L. Garner

  3. Nanovis Inc., West Lafayette, IN, USA

    David A. Detwiler & James McCarthy

  4. Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA

    Rusha Pal & Mohamed N. Seleem

  5. School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, USA

    Allen L. Garner

Authors
  1. Ram Anand Vadlamani
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  2. Agni Dhanabal
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  3. David A. Detwiler
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  4. Rusha Pal
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  5. James McCarthy
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  6. Mohamed N. Seleem
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  7. Allen L. Garner
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Contributions

R. A.V., D. A. D., A. D., J. M., M. N. S., and A. L. G designed research; R. A. V., D. A. D, A. D., and R. P. performed research; R. A. V., D. A. D, A. D., and A. L. G. analyzed data; and R. A. V., A. D., D. A. D., and A. L. G. wrote the paper.

Corresponding author

Correspondence to Allen L. Garner.

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Vadlamani, R.A., Dhanabal, A., Detwiler, D.A. et al. Nanosecond electric pulses rapidly enhance the inactivation of Gram-negative bacteria using Gram-positive antibiotics. Appl Microbiol Biotechnol 104, 2217–2227 (2020). https://doi.org/10.1007/s00253-020-10365-w

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  • DOI: https://doi.org/10.1007/s00253-020-10365-w

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