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*, Members of the One Day in Denmark (ODiD) Consortium

*Corresponding author for this work

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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.
Original languageEnglish
Article number1120023
JournalFrontiers in Microbiology
Volume14
Number of pages15
ISSN1664-302X
DOIs
Publication statusPublished - 2023

Keywords

  • Penicillin-binding proteins
  • Penicillin
  • Genotypic susceptibility
  • Pneumococcus
  • Streptococcus

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