title: Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA.
abstract: OBJECTIVE
  Our objective was to evaluate and exploit a whole genome sequence (WGS) bioinformatics pipeline for predicting antimicrobial resistance and capsular serotypes from invasive group B streptococci (iGBS).
  
  
  METHODS
  For 1975 iGBS recovered during 2015 from CDC's Active Bacterial Core surveillance, we compared pipeline predictions with broth dilution testing. Fifty-six isolates from earlier surveillance were included for testing β-lactams. Conventional serotyping was compared to WGS-based assignments for 302 isolates.
  
  
  RESULTS
  All 28 isolates with reduced susceptibility to β-lactam antibiotics harboured one of 19 rare PBP2x types. Resistances to erythromycin/clindamycin (808/1975 isolates, 41.0%), erythromycin (235/1975, 11.9%) and lincosamide/streptogramin A/pleuromutilins (56/1975, 2.8%) were predicted by the presence of erm-methylase, mef and lsa determinants, respectively (41 of 56 lsa gene-positive isolates also contained lnu, erm and/or mef genes). Presence of both erm and lsa determinants (25 isolates) predicted non-susceptibility to quinupristin/dalfopristin. Most isolates (1680/1975, 85.1%) were tet gene-positive, although 41/1565 (2.6%) tetM-positive isolates were tetracycline-susceptible. All 53 fluoroquinolone-resistant isolates contained ParC and/or GyrA substitutions. Resistances to rifampin (eight isolates), trimethoprim, chloramphenicol and vancomycin (two isolates each) were predicted by the pipeline. Resistance to macrolides/lincosamides without pipeline prediction was rare and correlated to divergent resistance genes or rRNA A2062G substitution. A selection of 267 isolates assigned WGS-based serotypes were also conventionally serotyped. Of these, 246 (92.1%) were in agreement, with the remaining 21 (7.8%) conventionally non-serotypeable. For 32 of 1975 isolates (1.6%), WGS-based serotypes could not be assigned.
  
  
  CONCLUSIONS
  The WGS-based assignment of iGBS resistance features and serotypes is an accurate substitute for phenotypic testing.
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Metcalf
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chochua
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gertz
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Hawkins
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ricaldi
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Walker
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tran
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rivers
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mathis
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Jackson
authors.affiliation: Minnesota Department of Health, St Paul, MN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Glennen
authors.affiliation: Minnesota Department of Health, St Paul, MN, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lynfield
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: L
authors.initials: L
authors.lastname: McGee
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: bbeall@cdc.gov.
authors.forename: B
authors.initials: B
authors.lastname: Beall
mesh_terms: D016667:Bacterial Capsules / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing / Q000379:methods*; D065288:Serogroup; D012703:Serotyping; D013292:Streptococcus agalactiae / Q000145:classification* / Q000187:drug effects* / Q000235:genetics; D014481:United States; D000073336:Whole Genome Sequencing / Q000379:methods*
keywords: Accessory and core resistome; Antimicrobial susceptibility testing; Capsular serotyping; Group B streptococci; Whole genome sequence