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Evaluation of peptide-based probes towards in vivo diagnostic imaging of bacterial biofilm-associated infections

Evaluation of peptide-based probes towards in vivo diagnostic imaging of bacterial biofilm-associated infections
Evaluation of peptide-based probes towards in vivo diagnostic imaging of bacterial biofilm-associated infections
The clinical management of bacterial biofilm infections represents an enormous challenge in today’s healthcare setting. The NIH estimates that 65% of bacterial infections are biofilm related and therapeutic outcomes are positively correlated with early intervention. Currently, there is no reliable imaging technique to detect biofilm infections in vivo and current clinical protocols for accurate and direct biofilm identification are non-existent. In orthopedic implant-associated biofilm infections, for example, current detection methods are based on non-specific X-ray or radiolabeled white blood cell imaging, coupled with peri-prosthetic tissue or fluid samples taken invasively and must be cultured. This approach is time consuming and often fails to detect biofilm bacteria due to sampling errors and lack of sensitivity. The ability to quantify bacterial biofilms by real-time, non-invasive imaging is an urgent, unmet clinical need that would revolutionize the management and treatment of these devastating types of infections. In the present study, we assembled a collection of fluorescently labeled peptide candidates to specifically explore their biofilm targeting properties. We evaluated these fluorescently labeled peptides using various in vitro assays for their ability to specifically and non-destructively target biofilms produced by the model bacterial pathogen Pseudomonas aeruginosa. The lead candidate that emerged, 4Iphf-HN17, demonstrated rapid biofilm labeling kinetics, a lack of bactericidal activity, and biofilm targeting specificity in human cell infection models. In vivo, fluorescently labeled 4Iphf-HN17 showed enhanced accumulation in biofilm-infected wounds, thus warranting further study.
Pseudomonas aeruginosa, biofilms, diagnostics, imaging, optical, peptides
2373-8227
2086-2098
Locke, Landon W.
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Shankaran, Kothandaraman
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Gong, Li
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Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Vozar, Samuel L.
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Cole, Sara L.
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Tweedle, Michael F.
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Wozniak, Daniel J.
bfa8e8e5-5929-449b-af6a-ec2d86c47eb5
Locke, Landon W.
6c9b1992-e200-405d-9f7b-c235ed0b8318
Shankaran, Kothandaraman
952db8c4-4df5-4b92-82d1-46d47d2b5a48
Gong, Li
48d59b22-33cf-47a8-a5da-df9e54840870
Stoodley, Paul
08614665-92a9-4466-806e-20c6daeb483f
Vozar, Samuel L.
9bd8a219-d103-4392-b454-97d5b0b7a3dd
Cole, Sara L.
ffa784dd-f18a-4d16-9e45-31625c236588
Tweedle, Michael F.
8ed41ad7-87b0-41a8-9efc-6e4c6022f2e7
Wozniak, Daniel J.
bfa8e8e5-5929-449b-af6a-ec2d86c47eb5

Locke, Landon W., Shankaran, Kothandaraman, Gong, Li, Stoodley, Paul, Vozar, Samuel L., Cole, Sara L., Tweedle, Michael F. and Wozniak, Daniel J. (2020) Evaluation of peptide-based probes towards in vivo diagnostic imaging of bacterial biofilm-associated infections. ACS Infectious Diseases, 6 (8), 2086-2098. (doi:10.1021/acsinfecdis.0c00125).

Record type: Article

Abstract

The clinical management of bacterial biofilm infections represents an enormous challenge in today’s healthcare setting. The NIH estimates that 65% of bacterial infections are biofilm related and therapeutic outcomes are positively correlated with early intervention. Currently, there is no reliable imaging technique to detect biofilm infections in vivo and current clinical protocols for accurate and direct biofilm identification are non-existent. In orthopedic implant-associated biofilm infections, for example, current detection methods are based on non-specific X-ray or radiolabeled white blood cell imaging, coupled with peri-prosthetic tissue or fluid samples taken invasively and must be cultured. This approach is time consuming and often fails to detect biofilm bacteria due to sampling errors and lack of sensitivity. The ability to quantify bacterial biofilms by real-time, non-invasive imaging is an urgent, unmet clinical need that would revolutionize the management and treatment of these devastating types of infections. In the present study, we assembled a collection of fluorescently labeled peptide candidates to specifically explore their biofilm targeting properties. We evaluated these fluorescently labeled peptides using various in vitro assays for their ability to specifically and non-destructively target biofilms produced by the model bacterial pathogen Pseudomonas aeruginosa. The lead candidate that emerged, 4Iphf-HN17, demonstrated rapid biofilm labeling kinetics, a lack of bactericidal activity, and biofilm targeting specificity in human cell infection models. In vivo, fluorescently labeled 4Iphf-HN17 showed enhanced accumulation in biofilm-infected wounds, thus warranting further study.

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ACS Locke Manu Revised_Clean (1) - Accepted Manuscript
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Accepted/In Press date: 14 June 2020
e-pub ahead of print date: 30 June 2020
Keywords: Pseudomonas aeruginosa, biofilms, diagnostics, imaging, optical, peptides

Identifiers

Local EPrints ID: 442526
URI: http://eprints.soton.ac.uk/id/eprint/442526
ISSN: 2373-8227
PURE UUID: 3dbd660f-0ab2-4211-a00d-701834b83a58
ORCID for Paul Stoodley: ORCID iD orcid.org/0000-0001-6069-273X

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Date deposited: 17 Jul 2020 16:31
Last modified: 23 Jul 2022 04:56

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Contributors

Author: Landon W. Locke
Author: Kothandaraman Shankaran
Author: Li Gong
Author: Paul Stoodley ORCID iD
Author: Samuel L. Vozar
Author: Sara L. Cole
Author: Michael F. Tweedle
Author: Daniel J. Wozniak

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