Multistate, population-based distributions of candidate vaccine targets, clonal complexes, and resistance features of invasive Group B Streptococci within the US: 2015-2017.

BACKGROUND Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS Using whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states. RESULTS Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2µg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS This first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

[1]  S. Madhi,et al.  The role of immune correlates of protection on the pathway to licensure, policy decision and use of group B Streptococcus vaccines for maternal immunization: considerations from World Health Organization consultations , 2019, Vaccine.

[2]  W. Schaffner,et al.  Epidemiology of Invasive Group B Streptococcal Infections Among Nonpregnant Adults in the United States, 2008-2016 , 2019, JAMA internal medicine.

[3]  D. Kasper,et al.  Surface Structures of Group B Streptococcus Important in Human Immunity , 2019, Microbiology spectrum.

[4]  W. Schaffner,et al.  Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015: Multistate Laboratory and Population-Based Surveillance , 2019, JAMA pediatrics.

[5]  Chang Ki Kim,et al.  First Case in Korea of Group B Streptococcus With Reduced Penicillin Susceptibility Harboring Amino Acid Substitutions in Penicillin-Binding Protein 2X , 2019, Annals of laboratory medicine.

[6]  K. Jansen,et al.  A Novel Hexavalent Capsular Polysaccharide Conjugate Vaccine (GBS6) for the Prevention of Neonatal Group B Streptococcal Infections by Maternal Immunization , 2019, The Journal of infectious diseases.

[7]  F. Kikkawa,et al.  Isolation of group B Streptococcus with reduced β-lactam susceptibility from pregnant women , 2019, Emerging microbes & infections.

[8]  M. Payne,et al.  Perinatal Streptococcus agalactiae Epidemiology and Surveillance Targets , 2018, Clinical Microbiology Reviews.

[9]  S. Madhi,et al.  Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-analyses , 2017, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  W. Schaffner,et al.  Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA. , 2017, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[11]  L. Westblade,et al.  Cross-resistance to lincosamides, streptogramins A and pleuromutilins in Streptococcus agalactiae isolates from the USA , 2017, The Journal of antimicrobial chemotherapy.

[12]  D. Di Gioia,et al.  Influence of Intrapartum Antibiotic Prophylaxis for Group B Streptococcus on Gut Microbiota in the First Month of Life , 2016, Journal of pediatric gastroenterology and nutrition.

[13]  W. Schaffner,et al.  Twenty Years of Active Bacterial Core Surveillance , 2015, Emerging infectious diseases.

[14]  K. Kimura,et al.  Classification of group B streptococci with reduced β-lactam susceptibility (GBS-RBS) based on the amino acid substitutions in PBPs. , 2015, The Journal of antimicrobial chemotherapy.

[15]  K. Dewar,et al.  Population Structure and Antimicrobial Resistance of Invasive Serotype IV Group B Streptococcus, Toronto, Ontario, Canada , 2015, Emerging infectious diseases.

[16]  Yong-hong Yang,et al.  Serotypes, Antibiotic Susceptibilities, and Multi-Locus Sequence Type Profiles of Streptococcus agalactiae Isolates Circulating in Beijing, China , 2015, PloS one.

[17]  J. Afset,et al.  Survey of Immunological Features of the Alpha-Like Proteins of Streptococcus agalactiae , 2014, Clinical and Vaccine Immunology.

[18]  S. Schrag,et al.  vanG Element Insertions within a Conserved Chromosomal Site Conferring Vancomycin Resistance to Streptococcus agalactiae and Streptococcus anginosus , 2014, mBio.

[19]  J. Rolain,et al.  ARG-ANNOT, a New Bioinformatic Tool To Discover Antibiotic Resistance Genes in Bacterial Genomes , 2013, Antimicrobial Agents and Chemotherapy.

[20]  S. Schrag,et al.  Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: experience in the United States and implications for a potential group B streptococcal vaccine. , 2013, Vaccine.

[21]  K. Kimura,et al.  High cephalosporin resistance due to amino acid substitutions in PBP1A and PBP2X in a clinical isolate of group B Streptococcus. , 2013, The Journal of antimicrobial chemotherapy.

[22]  R. Lynfield,et al.  Serotype IV and Invasive Group B Streptococcus Disease in Neonates, Minnesota, USA, 2000–2010 , 2013, Emerging infectious diseases.

[23]  S. Rasmussen,et al.  Identification of acquired antimicrobial resistance genes , 2012, The Journal of antimicrobial chemotherapy.

[24]  M. Bolognesi,et al.  Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections , 2011, Proceedings of the National Academy of Sciences.

[25]  Martin C. J. Maiden,et al.  BIGSdb: Scalable analysis of bacterial genome variation at the population level , 2010, BMC Bioinformatics.

[26]  S. Dramsi,et al.  The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates , 2010, The Journal of experimental medicine.

[27]  Daniel R Zerbino,et al.  Using the Velvet de novo Assembler for Short‐Read Sequencing Technologies , 2010, Current protocols in bioinformatics.

[28]  A. Coffey,et al.  Emergence of group B Streptococcus serotype IV in women of child-bearing age in Ireland , 2010, Epidemiology and Infection.

[29]  V. Nizet,et al.  The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood-brain barrier. , 2009, The Journal of infectious diseases.

[30]  V. Nizet,et al.  Point Mutation in the Group B Streptococcal pbp2x Gene Conferring Decreased Susceptibility to β-Lactam Antibiotics , 2008, Antimicrobial Agents and Chemotherapy.

[31]  K. Kimura,et al.  First Molecular Characterization of Group B Streptococci with Reduced Penicillin Susceptibility , 2008, Antimicrobial Agents and Chemotherapy.

[32]  E. Johnsson,et al.  Nonimmunodominant regions are effective as building blocks in a streptococcal fusion protein vaccine. , 2007, Cell host & microbe.

[33]  I. Margarit,et al.  Identification of novel genomic islands coding for antigenic pilus‐like structures in Streptococcus agalactiae , 2006, Molecular microbiology.

[34]  H. Tettelin,et al.  Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen , 2005, Science.

[35]  Gustavo Glusman,et al.  Structural and Genetic Diversity of Group B Streptococcus Capsular Polysaccharides , 2005, Infection and Immunity.

[36]  W. Hanage,et al.  eBURST: Inferring Patterns of Evolutionary Descent among Clusters of Related Bacterial Genotypes from Multilocus Sequence Typing Data , 2004, Journal of bacteriology.

[37]  G. Lindahl,et al.  Experimental vaccination against group B streptococcus, an encapsulated bacterium, with highly purified preparations of cell surface proteins Rib and alpha , 1996, Infection and immunity.

[38]  M. Pearlman Prevention of early-onset group B streptococcal disease in newborns. , 2003, Obstetrics and gynecology.

[39]  I. Margarit,et al.  Preventing bacterial infections with pilus-based vaccines: the group B streptococcus paradigm. , 2009, The Journal of infectious diseases.

[40]  N. Khardori Preventing Bacterial Infections with Pilus-Based Vaccines: the Group B Streptococcus Paradigm , 2009 .