AUTHOR=Eriksen Helle Brander , Fuursted Kurt , Jensen Anders , Jensen Christian Salgård , Nielsen Xiaohui , Christensen Jens Jørgen , Shewmaker Patricia , Rebelo Ana Rita , Aarestrup Frank Møller , Schønning Kristian , Slotved Hans-Christian ,  the One Day in Denmark (ODiD) Consortium 

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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1120023

DOI=10.3389/fmicb.2023.1120023

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>For <italic>Streptococcus pneumoniae</italic>, 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-<italic>S. pneumoniae</italic> Mitis-group streptococci (MGS) have similar PBPs and exchange <italic>pbp</italic>-alleles with <italic>S. pneumoniae</italic>. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish <italic>S. pneumoniae</italic> isolates and in internationally collected MGS.</p></sec><sec><title>Method</title><p>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.</p></sec><sec><title>Results</title><p>Among 88 <italic>S. pneumoniae</italic> isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 <italic>S. pneumoniae</italic> isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the <italic>S. pneumoniae</italic> database to non-<italic>S. pneumoniae</italic> MGS revealed that none had a recognized PBP-profile. For <italic>Streptococcus pseudopneumoniae</italic>, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 <italic>Streptococcus mitis</italic> isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 <italic>Streptococcus oralis</italic> isolates CA was 8% (penicillin) and 100% (ceftriaxone).</p></sec><sec><title>Conclusion</title><p>Using a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish <italic>S. pneumoniae</italic> isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.</p></sec>