Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide
Bacteria encased in a biofilm poses significant challenges to successful treatment, since both the immune system and antibiotics are ineffective. Sonobactericide, which uses ultrasound and microbubbles, is a potential new strategy for increasing antimicrobial effectiveness or directly killing bacter...
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MDPI AG
2022-05-01
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Online Access: | https://www.mdpi.com/1999-4923/14/6/1164 |
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author | Kirby R. Lattwein Inés Beekers Joop J. P. Kouijzer Mariël Leon-Grooters Simone A. G. Langeveld Tom van Rooij Antonius F. W. van der Steen Nico de Jong Willem J. B. van Wamel Klazina Kooiman |
author_facet | Kirby R. Lattwein Inés Beekers Joop J. P. Kouijzer Mariël Leon-Grooters Simone A. G. Langeveld Tom van Rooij Antonius F. W. van der Steen Nico de Jong Willem J. B. van Wamel Klazina Kooiman |
author_sort | Kirby R. Lattwein |
collection | DOAJ |
description | Bacteria encased in a biofilm poses significant challenges to successful treatment, since both the immune system and antibiotics are ineffective. Sonobactericide, which uses ultrasound and microbubbles, is a potential new strategy for increasing antimicrobial effectiveness or directly killing bacteria. Several studies suggest that sonobactericide can lead to bacterial dispersion or sonoporation (i.e., cell membrane permeabilization); however, real-time observations distinguishing individual bacteria during and directly after insonification are missing. Therefore, in this study, we investigated, in real-time and at high-resolution, the effects of ultrasound-induced microbubble oscillation on <i>Staphylococcus aureus</i> biofilms, without or with an antibiotic (oxacillin, 1 μg/mL). Biofilms were exposed to ultrasound (2 MHz, 100–400 kPa, 100–1000 cycles, every second for 30 s) during time-lapse confocal microscopy recordings of 10 min. Bacterial responses were quantified using post hoc image analysis with particle counting. Bacterial dispersion was observed as the dominant effect over sonoporation, resulting from oscillating microbubbles. Increasing pressure and cycles both led to significantly more dispersion, with the highest pressure leading to the most biofilm removal (up to 83.7%). Antibiotic presence led to more variable treatment responses, yet did not significantly impact the therapeutic efficacy of sonobactericide, suggesting synergism is not an immediate effect. These findings elucidate the direct effects induced by sonobactericide to best utilize its potential as a biofilm treatment strategy. |
first_indexed | 2024-03-09T22:46:11Z |
format | Article |
id | doaj.art-26188fea512347ef8d621d7be333d889 |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-09T22:46:11Z |
publishDate | 2022-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
spelling | doaj.art-26188fea512347ef8d621d7be333d8892023-11-23T18:29:19ZengMDPI AGPharmaceutics1999-49232022-05-01146116410.3390/pharmaceutics14061164Dispersing and Sonoporating Biofilm-Associated Bacteria with SonobactericideKirby R. Lattwein0Inés Beekers1Joop J. P. Kouijzer2Mariël Leon-Grooters3Simone A. G. Langeveld4Tom van Rooij5Antonius F. W. van der Steen6Nico de Jong7Willem J. B. van Wamel8Klazina Kooiman9Department of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center Rotterdam, Office Na9182, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsDepartment of Biomedical Engineering, Thoraxcenter, Erasmus MC University Medical Center Rotterdam, Office Ee2302, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsBacteria encased in a biofilm poses significant challenges to successful treatment, since both the immune system and antibiotics are ineffective. Sonobactericide, which uses ultrasound and microbubbles, is a potential new strategy for increasing antimicrobial effectiveness or directly killing bacteria. Several studies suggest that sonobactericide can lead to bacterial dispersion or sonoporation (i.e., cell membrane permeabilization); however, real-time observations distinguishing individual bacteria during and directly after insonification are missing. Therefore, in this study, we investigated, in real-time and at high-resolution, the effects of ultrasound-induced microbubble oscillation on <i>Staphylococcus aureus</i> biofilms, without or with an antibiotic (oxacillin, 1 μg/mL). Biofilms were exposed to ultrasound (2 MHz, 100–400 kPa, 100–1000 cycles, every second for 30 s) during time-lapse confocal microscopy recordings of 10 min. Bacterial responses were quantified using post hoc image analysis with particle counting. Bacterial dispersion was observed as the dominant effect over sonoporation, resulting from oscillating microbubbles. Increasing pressure and cycles both led to significantly more dispersion, with the highest pressure leading to the most biofilm removal (up to 83.7%). Antibiotic presence led to more variable treatment responses, yet did not significantly impact the therapeutic efficacy of sonobactericide, suggesting synergism is not an immediate effect. These findings elucidate the direct effects induced by sonobactericide to best utilize its potential as a biofilm treatment strategy.https://www.mdpi.com/1999-4923/14/6/1164antibioticbacteriabiofilmdispersionmicrobubblesonobactericide |
spellingShingle | Kirby R. Lattwein Inés Beekers Joop J. P. Kouijzer Mariël Leon-Grooters Simone A. G. Langeveld Tom van Rooij Antonius F. W. van der Steen Nico de Jong Willem J. B. van Wamel Klazina Kooiman Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide Pharmaceutics antibiotic bacteria biofilm dispersion microbubble sonobactericide |
title | Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide |
title_full | Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide |
title_fullStr | Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide |
title_full_unstemmed | Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide |
title_short | Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide |
title_sort | dispersing and sonoporating biofilm associated bacteria with sonobactericide |
topic | antibiotic bacteria biofilm dispersion microbubble sonobactericide |
url | https://www.mdpi.com/1999-4923/14/6/1164 |
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