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Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing

Since conventional culture-based antibiotic susceptibility testing (AST) methods are too time-consuming (typically 24–72 h), rapid AST is urgently needed for preventing the increasing emergence and spread of antibiotic resistant infections. Although several phenotypic antibiotic resistance sensing m...

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Autores principales: Song, Donghui, Liu, Haomin, Ji, Huayi, Lei, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651422/
https://www.ncbi.nlm.nih.gov/pubmed/31277201
http://dx.doi.org/10.3390/molecules24132441
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author Song, Donghui
Liu, Haomin
Ji, Huayi
Lei, Yu
author_facet Song, Donghui
Liu, Haomin
Ji, Huayi
Lei, Yu
author_sort Song, Donghui
collection PubMed
description Since conventional culture-based antibiotic susceptibility testing (AST) methods are too time-consuming (typically 24–72 h), rapid AST is urgently needed for preventing the increasing emergence and spread of antibiotic resistant infections. Although several phenotypic antibiotic resistance sensing modalities are able to reduce the AST time to a few hours or less, concerning the biological heterogeneity, their accuracy or limit of detection are limited by low throughput. Here, we present a rapid AST method based on whole slide imaging (WSI)-enabled high-throughput sensing antibiotic resistance at single-bacterium level. The time for determining the minimum inhibitory concentration (MIC) was theoretically shortest, which ensures that the growth of each individual cell present in a large population is inhibited. As a demonstration, our technique was able to sense the growth of at least several thousand bacteria at single-cell level. Reliable MIC of Enterobacter cloacae against gentamicin was obtained within 1 h, while the gold standard broth dilution method required at least 16 h for the same result. In addition, the application of our method prevails over other imaging-based AST approaches in allowing rapid and accurate determination of antibiotic susceptibility for phenotypically heterogeneous samples, in which the number of antibiotic resistant cells was negligible compared to that of the susceptible cells. Hence, our method shows great promise for both rapid AST determination and point-of-care testing of complex clinical bacteria isolates.
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spelling pubmed-66514222019-08-08 Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing Song, Donghui Liu, Haomin Ji, Huayi Lei, Yu Molecules Article Since conventional culture-based antibiotic susceptibility testing (AST) methods are too time-consuming (typically 24–72 h), rapid AST is urgently needed for preventing the increasing emergence and spread of antibiotic resistant infections. Although several phenotypic antibiotic resistance sensing modalities are able to reduce the AST time to a few hours or less, concerning the biological heterogeneity, their accuracy or limit of detection are limited by low throughput. Here, we present a rapid AST method based on whole slide imaging (WSI)-enabled high-throughput sensing antibiotic resistance at single-bacterium level. The time for determining the minimum inhibitory concentration (MIC) was theoretically shortest, which ensures that the growth of each individual cell present in a large population is inhibited. As a demonstration, our technique was able to sense the growth of at least several thousand bacteria at single-cell level. Reliable MIC of Enterobacter cloacae against gentamicin was obtained within 1 h, while the gold standard broth dilution method required at least 16 h for the same result. In addition, the application of our method prevails over other imaging-based AST approaches in allowing rapid and accurate determination of antibiotic susceptibility for phenotypically heterogeneous samples, in which the number of antibiotic resistant cells was negligible compared to that of the susceptible cells. Hence, our method shows great promise for both rapid AST determination and point-of-care testing of complex clinical bacteria isolates. MDPI 2019-07-03 /pmc/articles/PMC6651422/ /pubmed/31277201 http://dx.doi.org/10.3390/molecules24132441 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Song, Donghui
Liu, Haomin
Ji, Huayi
Lei, Yu
Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing
title Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing
title_full Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing
title_fullStr Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing
title_full_unstemmed Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing
title_short Whole Slide Imaging for High-Throughput Sensing Antibiotic Resistance at Single-Bacterium Level and Its Application to Rapid Antibiotic Susceptibility Testing
title_sort whole slide imaging for high-throughput sensing antibiotic resistance at single-bacterium level and its application to rapid antibiotic susceptibility testing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651422/
https://www.ncbi.nlm.nih.gov/pubmed/31277201
http://dx.doi.org/10.3390/molecules24132441
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