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Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data

Prediction of antibiotic resistance from whole genome sequence (WGS) data has been proposed. However, the performance of WGS data analysis for this matter may be influenced by the resistance mechanism’s biology. This study compared traditional antimicrobial susceptibility testing with whole genome s...

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Autores principales: Heydecke, Anna, Yin, Hong, Tano, Eva, Sütterlin, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688838/
https://www.ncbi.nlm.nih.gov/pubmed/38033151
http://dx.doi.org/10.1371/journal.pone.0295233
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author Heydecke, Anna
Yin, Hong
Tano, Eva
Sütterlin, Susanne
author_facet Heydecke, Anna
Yin, Hong
Tano, Eva
Sütterlin, Susanne
author_sort Heydecke, Anna
collection PubMed
description Prediction of antibiotic resistance from whole genome sequence (WGS) data has been proposed. However, the performance of WGS data analysis for this matter may be influenced by the resistance mechanism’s biology. This study compared traditional antimicrobial susceptibility testing with whole genome sequencing for identification of extended-spectrum beta-lactamases (ESBL) in a collection of 419 Escherichia coli isolates. BLASTn-based prediction and read mapping with srst2 gave matching results, and in 381/419 (91%) isolates WGS was congruent with phenotypic testing. Incongruent results were grouped by potential explanations into biological-related and sequence analysis-related results. Biological-related explanations included weak ESBL-enzyme activity (n = 4), inconclusive phenotypic ESBL-testing (n = 4), potential loss of plasmid during subculturing (n = 7), and other resistance mechanisms than ESBL-enzymes (n = 2). Sequence analysis-related explanations were cut-off dependency for read depth (n = 5), too stringent (n = 3) and too loose cut-off for nucleotide identity and coverage (n = 13), respectively. The results reveal limitations of both traditional antibiotic susceptibility testing and sequence-based resistance prediction and highlight the need for evidence-based standards in sequence analysis.
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spelling pubmed-106888382023-12-01 Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data Heydecke, Anna Yin, Hong Tano, Eva Sütterlin, Susanne PLoS One Research Article Prediction of antibiotic resistance from whole genome sequence (WGS) data has been proposed. However, the performance of WGS data analysis for this matter may be influenced by the resistance mechanism’s biology. This study compared traditional antimicrobial susceptibility testing with whole genome sequencing for identification of extended-spectrum beta-lactamases (ESBL) in a collection of 419 Escherichia coli isolates. BLASTn-based prediction and read mapping with srst2 gave matching results, and in 381/419 (91%) isolates WGS was congruent with phenotypic testing. Incongruent results were grouped by potential explanations into biological-related and sequence analysis-related results. Biological-related explanations included weak ESBL-enzyme activity (n = 4), inconclusive phenotypic ESBL-testing (n = 4), potential loss of plasmid during subculturing (n = 7), and other resistance mechanisms than ESBL-enzymes (n = 2). Sequence analysis-related explanations were cut-off dependency for read depth (n = 5), too stringent (n = 3) and too loose cut-off for nucleotide identity and coverage (n = 13), respectively. The results reveal limitations of both traditional antibiotic susceptibility testing and sequence-based resistance prediction and highlight the need for evidence-based standards in sequence analysis. Public Library of Science 2023-11-30 /pmc/articles/PMC10688838/ /pubmed/38033151 http://dx.doi.org/10.1371/journal.pone.0295233 Text en © 2023 Heydecke et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Heydecke, Anna
Yin, Hong
Tano, Eva
Sütterlin, Susanne
Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
title Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
title_full Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
title_fullStr Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
title_full_unstemmed Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
title_short Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
title_sort limitations in predicting reduced susceptibility to third generation cephalosporins in escherichia coli based on whole genome sequence data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688838/
https://www.ncbi.nlm.nih.gov/pubmed/38033151
http://dx.doi.org/10.1371/journal.pone.0295233
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