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Genomic Analyses of Pneumococci from Children with Sickle Cell Disease Expose Host-Specific Bacterial Adaptations and Deficits in Current Interventions

journal contribution
posted on 2023-02-07, 23:50 authored by Robert Carter, Joshua Wolf, Tim van Opijnen, Martha Muller, Caroline Obert, Corinna Burnham, Beth Mann, Yimei Li, Randall T Hayden, Tamara Pestina, Derek Persons, Andrew Camilli, Patricia M Flynn, Elaine I Tuomanen, Jason W Rosch
Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of more than 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism, and metal transport. A murine SCD model coupled with Tn-seq mutagenesis identified 60 noncapsular pneumococcal genes under differential selective pressure in SCD, which correlated with aspects of SCD pathophysiology. Further, virulence determinants in the SCD context were distinct from the general population, and protective capacity of potential antigens was lost over time in SCD. This highlights the importance of understanding bacterial pathogenesis in the context of high-risk individuals.

History

Journal

CELL HOST & MICROBE

Volume

15

Pagination

587-599

Location

United States

ISSN

1931-3128

eISSN

1934-6069

Language

English

Issue

5

Publisher

CELL PRESS