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2021 OMIG Abstract
Population Structure of Ocular Streptococcus pneumoniae is Highly Diverse and Formed by Lineages that Escape Current Vaccines
Camille André1,2, John Rouhana2, Suelen S. de Mello2, Gabriela R. da Cunha2, Andrew G. Van Camp2, Michael S. Gilmore1,2,3 and Paulo J. M. Bispo1,2
1Infectious Disease Institute, 2Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA; and 3 Department of Microbiology and Immunobiology, Harvard Medical School,
Boston, MA
Purpose: Streptococcus pneumoniae is leading cause of ocular infections including serious and sight-threatening conditions. The use of pneumococcal conjugate vaccines (PCV) has substantially reduced the incidence of pneumonia and invasive pneumococcal diseases, but has had limited impact on ocular infections. Additionally, widespread vaccine use has resulted in ongoing selective pressure and serotype replacement in carriage and disease. To gain insight into the population structure of pneumococcal isolates causing ocular infections in a post-PCV-13 time period, we investigated the genomic epidemiology of ocular S. pneumoniae isolates collected at Massachusetts Eye and Ear between 2014 and 2017.
Methods: 45 consecutive isolates were characterized by whole genome sequencing (Illumina). We used CLC Genomics workbench to trim and assemble the sequences and the pipeline on Center for Genomic Epidemiology to obtain species identification, sequence type (ST) and the pool of acquired resistance genes. STs were grouped into clonal complexes (CC) using goeBURST. A SNP-based phylogenetic tree was reconstructed after removal of recombinant DNA segments using Parsnp Capsule serotype was predicted genomically using Pneumocat.
Results: We found that the population structure of ocular S. pneumoniae is highly diverse with 27 sequence types (grouped into 18 clonal complexes) and 17 serotypes being identified. Distribution of these lineages diverged according to the site of isolation, with conjunctivitis being commonly caused by strains grouped in the Epidemic Conjunctivitis Cluster-ECC (60%), and ST448 (53.3%) being most frequently identified. Conversely, S. pneumoniae keratitis cases were caused by a highly diverse population of isolates grouping within 13 different clonal complexes. Serotyping inference demonstrated that 95.5% of the isolates were non-PCV-13 vaccine types. Most of the conjunctivitis strains (80%) were unencapsulated, with the remaining belonging to serotypes 15B, 3 and 23B. On the other hand, S. pneumoniae causing keratitis were predominantly encapsulated (95.2%) with 13 different serotypes identified, mostly being non-vaccine types. Carriage of macrolide resistance genes was common in our ocular S. pneumoniae population (42.2%), and usually associated with the mefA + msrD genotype (n=15). These genes were located in the Macrolide Efflux Genetic Assembly cassette and were associated with low-level in vitro resistance to 14- and 15-membered macrolides. Less frequently, macrolide-resistant isolates carried an ermB gene (n=4), which was co-located with the tetM gene in a Tn-916-like transposon.
Conclusions: Our study demonstrates that the population structure of ocular S. pneumoniae is highly diverse, mainly composed by strains that scape the PCV-13 vaccine, with patterns of tissue/niche segregation, adaptation and specialization. These findings suggest that the population structure of ocular pneumococcus may be shaped by multiple factors including PCV-13 selective pressure, microbial-related and niche-specific host-associated features.
Disclosure: S
Support: Grants from NEI [EY031600 and EY024285]; and the Massachusetts Lions Eye Research Fund
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