Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms

Caudwell, Jack; Tinkler, Jordan M; Johnson, Ben R G; McDowall, Kenneth J.; Alsulaimani, Fayez; Tiede, Christian; Tomlinson, Darren; Freear, Steven; Turnbull, W. Bruce; Evans, Stephen D.; Sandoe, Jonathan

doi:10.1016/j.bioflm.2022.100074

Cited by 9 publications

(14 citation statements)

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“…On the other hand, enhanced microbubble displacement may result in less cell death, as reported in endothelial cells, where non-displacing microbubbles were more lethal [14]; although, it should be noted, again, that mammalian cells and S. aureus are very different cell types. To further understand the relationship between microbubble displacement and bacterial cell death and dispersion, a similar study, such as that of van Rooij et al [14], could be conducted using non-targeted and targeted microbubbles for bacterial biofilms, such as with the innovative, recently published targeted microbubbles using vancomycin [17] or Affimer protein [25]. Bacterial dispersal was a direct consequence of microbubble displacement and subsequent clustering, quantitatively supported in Figure 8, which was possibly due to secondary Bjerknes forces.…”

Section: Discussionmentioning

confidence: 83%

“…Sonobactericide has been demonstrated in several papers on Staphylococcus aureus (S. aureus) biofilms [17][18][19][20][21][22][23][24][25], which is the predominate infecting microbe for many types of infections, and it is associated with more severe disease, higher mortality, and longer hospital stays [26]. A range of effects, as a result of sonobactericide on S. aureus using non-targeted microbubbles, have been observed or suggested, including biofilm disruption/dispersal [19,21], sonoporation (not quantified) [23], and enhanced antimicrobial efficacy [19,21,23,24].…”

Section: Introductionmentioning

confidence: 99%

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Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide

et al. 2022

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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 Staphylococcus aureus 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.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide

et al. 2022

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“…The introduction of fluorescent small molecules can be confirmed by confocal microscopy (Figure 5f) [84,109,133,143,147], while STED or fluorescent lifetime imaging mi- For characterization of MB morphology, transmission electron cryomicroscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) methods were successfully implemented, examples are provided in Figure 5a-c, respectively [94,133,145,146]. SEM of broken MBs and AFM of dried MBs can provide precise information about MB shell thickness, as illustrated in Figure 5d,e, respectively [90,146].…”

Section: Advanced Characterization Of Mbs With a Protein Shellmentioning

confidence: 86%

“…The introduction of fluorescent small molecules can be confirmed by confocal microscopy (Figure 5f) [84,109,133,143,147], while STED or fluorescent lifetime imaging microscopy (FLIM) may offer higher image resolution combined with insight into the homogeneous/heterogeneous distribution of fluorescent components in the shell and distribution of dye among MB population (Figure 5g) [148]. Unfortunately, FLIM and STED methods are barely described for protein MBs [138].…”

Section: Advanced Characterization Of Mbs With a Protein Shellmentioning

confidence: 99%

Microbubbles Stabilized by Protein Shell: From Pioneering Ultrasound Contrast Agents to Advanced Theranostic Systems

et al. 2022

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Ultrasound is a widely-used imaging modality in clinics as a low-cost, non-invasive, non-radiative procedure allowing therapists faster decision-making. Microbubbles have been used as ultrasound contrast agents for decades, while recent attention has been attracted to consider them as stimuli-responsive drug delivery systems. Pioneering microbubbles were Albunex with a protein shell composed of human serum albumin, which entered clinical practice in 1993. However, current research expanded the set of proteins for a microbubble shell beyond albumin and applications of protein microbubbles beyond ultrasound imaging. Hence, this review summarizes all-known protein microbubbles over decades with a critical evaluation of formulations and applications to optimize the safety (low toxicity and high biocompatibility) as well as imaging efficiency. We provide a comprehensive overview of (1) proteins involved in microbubble formulation, (2) peculiarities of preparation of protein stabilized microbubbles with consideration of large-scale production, (3) key chemical factors of stabilization and functionalization of protein-shelled microbubbles, and (4) biomedical applications beyond ultrasound imaging (multimodal imaging, drug/gene delivery with attention to anticancer treatment, antibacterial activity, biosensing). Presented critical evaluation of the current state-of-the-art for protein microbubbles should focus the field on relevant strategies in microbubble formulation and application for short-term clinical translation. Thus, a protein bubble-based platform is very perspective for theranostic application in clinics.

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“…AClfA1-functionalized microbubbles showed marked biomass loss and a high dead cell count against S. aureus biofilms. 164 Ghosh et al (2021) showed that two types of conductive polymer nanofibers (CPNs) including polythiophene (PEDOT) and polyaniline (PANI) showed strong antimicrobial activity against E. coli and S. aureus biofilms. 165 The bactericidal activity of these CPNs is attributed to the generation of ROS (reactive oxygen species) induced by photostimulation, which can cause damage to the bacterial cell membranes and subsequently restrict biofilm formation.…”

Section: Metal and Metal Oxidementioning

confidence: 99%

Advances in Nanotechnology for Biofilm Inhibition

et al. 2023

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Biofilm-associated infections have emerged as a significant public health challenge due to their persistent nature and increased resistance to conventional treatment methods. The indiscriminate usage of antibiotics has made us susceptible to a range of multidrug-resistant pathogens. These pathogens show reduced susceptibility to antibiotics and increased intracellular survival. However, current methods for treating biofilms, such as smart materials and targeted drug delivery systems, have not been found effective in preventing biofilm formation. To address this challenge, nanotechnology has provided innovative solutions for preventing and treating biofilm formation by clinically relevant pathogens. Recent advances in nanotechnological strategies, including metallic nanoparticles, functionalized metallic nanoparticles, dendrimers, polymeric nanoparticles, cyclodextrin-based delivery, solid lipid nanoparticles, polymer drug conjugates, and liposomes, may provide valuable technological solutions against infectious diseases. Therefore, it is imperative to conduct a comprehensive review to summarize the recent advancements and limitations of advanced nanotechnologies. The present Review encompasses a summary of infectious agents, the mechanisms that lead to biofilm formation, and the impact of pathogens on human health. In a nutshell, this Review offers a comprehensive survey of the advanced nanotechnological solutions for managing infections. A detailed presentation has been made as to how these strategies may improve biofilm control and prevent infections. The key objective of this Review is to summarize the mechanisms, applications, and prospects of advanced nanotechnologies to provide a better understanding of their impact on biofilm formation by clinically relevant pathogens.

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Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms

Cited by 9 publications

References 74 publications

Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide

Dispersing and Sonoporating Biofilm-Associated Bacteria with Sonobactericide

Microbubbles Stabilized by Protein Shell: From Pioneering Ultrasound Contrast Agents to Advanced Theranostic Systems

Advances in Nanotechnology for Biofilm Inhibition

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