Comparative Genomics of Carriage and Disease Isolates of Streptococcus pneumoniae Serotype 22F Reveals Lineage-Specific Divergence and Niche Adaptation

• Published in: Genome biology and evolution Vol. 8; no. 4; pp. 1243 - 1251
• Main Authors: Cleary, David W, Devine, Vanessa T, Jefferies, Johanna M C, Webb, Jeremy S, Bentley, Stephen D, Gladstone, Rebecca A, Faust, Saul N, Clarke, Stuart C
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-04-2016
• Subjects: Amidohydrolases - genetics; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Child; Drug Resistance, Microbial; Female; Genome Report; Genome, Bacterial; Genomic Islands; Genomics; Genomics - methods; Humans; Male; Middle Aged; Mutation; Pneumococcal Infections - drug therapy; Pneumococcal Infections - microbiology; Streptococcus infections; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - isolation & purification; Streptococcus pneumoniae - pathogenicity; Virulence Factors - genetics; genome sequencing; invasive pneumococcal disease; Streptococcus pneumoniae
• ISSN: 1759-6653; 1759-6653
• DOI: 10.1093/gbe/evw066

Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom's childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin--antitoxin systems, were also observed.