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

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; One Day in Denmark (ODiD) Consortium

doi:10.3389/fmicb.2023.1120023

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

Front Microbiol. 2023 Mar 2:14:1120023. doi: 10.3389/fmicb.2023.1120023. eCollection 2023.

Affiliations

¹ Department of Clinical Microbiology, Herlev and Gentofte Hospital, Herlev, Denmark.
² Department of Bacteria, Parasites, and Fungi, Statens Serum Institut, Copenhagen, Denmark.
³ Department of Clinical Microbiology, Sygehus Lillebælt, Vejle, Denmark.
⁴ Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
⁵ The Regional Department of Clinical Microbiology, Slagelse, Denmark.
⁶ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁷ Centers for Disease Control and Prevention, Atlanta, GA, United States.
⁸ Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.

Abstract

Introduction: For 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.

Method: Isolates 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.

Results: Among 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).

Conclusion: Using 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.

Keywords: Streptococcus; genotypic susceptibility; penicillin; penicillin-binding proteins; pneumococcus.