Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci

IntroductionFor Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC)....

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Main Authors: Helle Brander Eriksen, Kurt Fuursted, Anders Jensen, Christian Salgård Jensen, Xiaohui Nielsen, Jens Jørgen Christensen, Patricia Shewmaker, Ana Rita Rebelo, Frank Møller Aarestrup, Kristian Schønning, Hans-Christian Slotved, the One Day in Denmark (ODiD) Consortium
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1120023/full
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author Helle Brander Eriksen
Kurt Fuursted
Anders Jensen
Christian Salgård Jensen
Xiaohui Nielsen
Xiaohui Nielsen
Jens Jørgen Christensen
Jens Jørgen Christensen
Patricia Shewmaker
Ana Rita Rebelo
Frank Møller Aarestrup
Kristian Schønning
Hans-Christian Slotved
the One Day in Denmark (ODiD) Consortium
author_facet Helle Brander Eriksen
Kurt Fuursted
Anders Jensen
Christian Salgård Jensen
Xiaohui Nielsen
Xiaohui Nielsen
Jens Jørgen Christensen
Jens Jørgen Christensen
Patricia Shewmaker
Ana Rita Rebelo
Frank Møller Aarestrup
Kristian Schønning
Hans-Christian Slotved
the One Day in Denmark (ODiD) Consortium
author_sort Helle Brander Eriksen
collection DOAJ
description IntroductionFor Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS.MethodIsolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression.ResultsAmong 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone).ConclusionUsing a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.
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spelling doaj.art-a8489f2c792242188a9c2b7d3f7d12252023-03-02T07:06:22ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-03-011410.3389/fmicb.2023.11200231120023Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococciHelle Brander Eriksen0Kurt Fuursted1Anders Jensen2Christian Salgård Jensen3Xiaohui Nielsen4Xiaohui Nielsen5Jens Jørgen Christensen6Jens Jørgen Christensen7Patricia Shewmaker8Ana Rita Rebelo9Frank Møller Aarestrup10Kristian Schønning11Hans-Christian Slotved12the One Day in Denmark (ODiD) ConsortiumDepartment of Clinical Microbiology, Herlev and Gentofte Hospital, Herlev, DenmarkDepartment of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, DenmarkDepartment of Clinical Microbiology, Sygehus Lillebælt, Vejle, DenmarkDepartment of Clinical Microbiology, Rigshospitalet, Copenhagen, DenmarkThe Regional Department of Clinical Microbiology, Slagelse, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkThe Regional Department of Clinical Microbiology, Slagelse, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkCenters for Disease Control and Prevention, Atlanta, GA, United StatesResearch Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kongens Lyngby, DenmarkResearch Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Clinical Microbiology, Rigshospitalet, Copenhagen, DenmarkDepartment of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, DenmarkIntroductionFor Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS.MethodIsolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression.ResultsAmong 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone).ConclusionUsing a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1120023/fullpenicillin-binding proteinspenicillingenotypic susceptibilitypneumococcusStreptococcus
spellingShingle Helle Brander Eriksen
Kurt Fuursted
Anders Jensen
Christian Salgård Jensen
Xiaohui Nielsen
Xiaohui Nielsen
Jens Jørgen Christensen
Jens Jørgen Christensen
Patricia Shewmaker
Ana Rita Rebelo
Frank Møller Aarestrup
Kristian Schønning
Hans-Christian Slotved
the One Day in Denmark (ODiD) Consortium
Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
Frontiers in Microbiology
penicillin-binding proteins
penicillin
genotypic susceptibility
pneumococcus
Streptococcus
title Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
title_full Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
title_fullStr Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
title_full_unstemmed Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
title_short Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci
title_sort predicting β lactam susceptibility from the genome of streptococcus pneumoniae and other mitis group streptococci
topic penicillin-binding proteins
penicillin
genotypic susceptibility
pneumococcus
Streptococcus
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1120023/full
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