Caroline M. Weight, United Kingdom
University College London NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection & ImmunityPresenter of 1 Presentation
MUTATIONS OF STREPTOCOCCUS PNEUMONIAE BIOSYNTHESIS GENES INFLUENCE EPITHELIAL MICRO-INVASION AND THE INNATE-EPITHELIAL CELL RESPONSE IN VITRO AND IN AN EXPERIMENTAL HUMAN PNEUMOCOCCAL CHALLENGE MODEL (ID 872)
- Caroline M. Weight, United Kingdom
- José-Afonso Guerra-Assuncao, United Kingdom
- Elisa Ramos-Sevillano, United Kingdom
- Annie Blizard, United Kingdom
- Jesus Reine, United Kingdom
- Madhad Noursadeghi, United Kingdom
- Daniela M. Ferreira, United Kingdom
- Jeremy Brown, United Kingdom
- Robert S. Heyderman, United Kingdom
Author Of 3 Presentations
NUTRITIONAL AND ENVIRONMENTAL REGULATION OF PNEUMOCOCCAL CENTRAL CARBON METABOLISM RELEVANT TO THE COMMENSAL-PATHOGEN INTERFACE. (ID 483)
INCREASE IN FREQUENCY OF PNEUMOCOCCAL METABOLIC GENOTYPES CHARACTERISED BY ANTIMICROBIAL RESISTANCE AND ADAPTATIONS FOR COLONIZATION AFTER PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 416)
- Andrea Gori, United Kingdom
- Uri Obolski, Israel
- Todd D. Swarthout, Malawi
- Jose Lourenço, United Kingdom
- Caroline M. Weight, United Kingdom
- Jen Cornick,
- Dean Everett, Malawi
- Arox Kamng'ona,
- Thandie S. Mwalukomo,
- Martin C. Maiden, United Kingdom
- Neil French, United Kingdom
- Sunetra Gupta, United Kingdom
- Robert S. Heyderman, United Kingdom
Abstract
Background
Streptococcus pneumoniae naturally undergoes fluctuations in genotype. We previously showed a high residual prevalence of vaccine serotype (VT) pneumococci (18% in under 5’s) 7 years after PCV13 introduction in Malawi. In this context, we hypothesised the emergence and fixation of S. pneumoniae lineages with genetic traits conveying a competitive advantage in the nasopharyngeal niche.
Methods
1826 S. pneumoniae genomes were analysed from isolates collected during rolling cross-sectional carriage surveys in Blantyre, 4-7 years after PCV13 introduction. The metabolic core-genome includes 175 discrete metabolic genotypic profiles (metabolic types, MTs). Relative fitness was assessed by in-vitro growth and adhesive potential evaluated using Detroit 562 nasopharyngeal epithelial cells.
Results
High residual pneumococcal carriage is characterised by persistent MTs in VT (e.g. 3 and 23F) and emerging new MTs in non-VT (NVT; 38 and 23B). Increase in AMR MTs among 38 and 23B was observed. Emerging MTs show characteristic sequences of virulence genes and are characterised phenotypically by higher growth potential and propensity for better adherence to NP cell. We identified convergent evolution between MTs isolated in different countries, result of genetic bottlenecks.
Conclusions
This shift in metabolic genotypes, antimicrobial resistance and colonization adaptations may facilitate vaccine escape.
MUTATIONS OF STREPTOCOCCUS PNEUMONIAE BIOSYNTHESIS GENES INFLUENCE EPITHELIAL MICRO-INVASION AND THE INNATE-EPITHELIAL CELL RESPONSE IN VITRO AND IN AN EXPERIMENTAL HUMAN PNEUMOCOCCAL CHALLENGE MODEL (ID 872)
- Caroline M. Weight, United Kingdom
- José-Afonso Guerra-Assuncao, United Kingdom
- Elisa Ramos-Sevillano, United Kingdom
- Annie Blizard, United Kingdom
- Jesus Reine, United Kingdom
- Madhad Noursadeghi, United Kingdom
- Daniela M. Ferreira, United Kingdom
- Jeremy Brown, United Kingdom
- Robert S. Heyderman, United Kingdom