title: Emergence of Amoxicillin-Resistant Variants of Spain9V-ST156 Pneumococci Expressing Serotype 11A Correlates with Their Ability to Evade the Host Immune Response.
abstract: Capsular switching allows pre-existing clones of Streptococcus pneumoniae expressing vaccine serotypes to escape the vaccine-induced immunity by acquisition of capsular genes from pneumococci of a non-vaccine serotype. Here, we have analysed the clonal composition of 492 clinical isolates of serotype 11A causing invasive disease in Spain (2000-2012), and their ability to evade the host immune response. Antibiograms, serotyping and molecular typing were performed. The restriction profiles of pbp2x, pbp1a and pbp2b genes were also analysed. Interaction with the complement components C1q, C3b, C4BP, and factor H was explored whereas opsonophagocytosis assays were performed using a human cell line differentiated to neutrophils. Biofilm formation and the polymorphisms of the major autolysin LytA were evaluated. The main genotypes of the 11A pneumococci were: ST62 (447 isolates, 90.6%), followed by ST6521 (35 isolates, 7.3%) and ST838 (10 isolates, 2.1%). Beta lactam resistant serotype 11A variants of genotypes ST838 and ST6521 closely related to the Spain9V-ST156 clone were first detected in 2005. A different pattern of evasion of complement immunity and phagocytosis was observed between genotypes. The emergence of one vaccine escape variant of Spain9V-ST156 (ST652111A), showing a high potential to avoid the host immune response, was observed. In addition, isolates of ST652111A showed higher ability to produce biofilms than ST83811A or ST6211A, which may have contributed to the emergence of this PEN-resistant ST652111A genotype in the last few years. The emergence of penicillin-resistant 11A invasive variants of the highly successful ST156 clonal complex merits close monitoring.
authors.affiliation: Spanish Pneumococcal Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Aguinagalde
authors.affiliation: Spanish Pneumococcal Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Corsini
authors.affiliation: Microbiology Department, Hospital Universitari de Bellvitge-IDIBELL-Barcelona University, Barcelona, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Domenech
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Centro de Investigaciones Biológicas-CSIC, Madrid, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Domenech
authors.affiliation: Microbiology Department, Hospital Universitari de Bellvitge-IDIBELL-Barcelona University, Barcelona, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Cámara
authors.affiliation: Microbiology Department, Hospital Universitari de Bellvitge-IDIBELL-Barcelona University, Barcelona, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ardanuy
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Centro de Investigaciones Biológicas-CSIC, Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: García
authors.affiliation: Microbiology Department, Hospital Universitari de Bellvitge-IDIBELL-Barcelona University, Barcelona, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Liñares
authors.affiliation: Spanish Pneumococcal Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: Fenoll
authors.affiliation: Spanish Pneumococcal Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Yuste
mesh_terms: D000293:Adolescent; D000328:Adult; D000658:Amoxicillin; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial / Q000235:genetics / Q000276:immunology; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D005838:Genotype; D018922:HL-60 Cells; D049690:History, Ancient; D006801:Humans; D057131:Immune Evasion; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D065288:Serogroup; D013030:Spain; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
chemical_list: D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D000658:Amoxicillin