Journal article
In vivo capsular switch in Streptococcus pneumoniae--analysis by whole genome sequencing
PloS one, v 7(11), pp e47983-e47983
2012
PMID: 23144841
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Two multidrug resistant strains of Streptococcus pneumoniae - SV35-T23 (capsular type 23F) and SV36-T3 (capsular type 3) were recovered from the nasopharynx of two adult patients during an outbreak of pneumococcal disease in a New York hospital in 1996. Both strains belonged to the pandemic lineage PMEN1 but they differed strikingly in virulence when tested in the mouse model of IP infection: as few as 1000 CFU of SV36 killed all mice within 24 hours after inoculation while SV35-T23 was avirulent.Whole genome sequencing (WGS) of the two isolates was performed (i) to test if these two isolates belonging to the same clonal type and recovered from an identical epidemiological scenario only differed in their capsular genes? and (ii) to test if the vast difference in virulence between the strains was mostly - or exclusively - due to the type III capsule. WGS demonstrated extensive differences between the two isolates including over 2500 single nucleotide polymorphisms in core genes and also differences in 36 genetic determinants: 25 of which were unique to SV35-T23 and 11 unique to strain SV36-T3. Nineteen of these differences were capsular genes and 9 bacteriocin genes.Using genetic transformation in the laboratory, the capsular region of SV35-T23 was replaced by the type 3 capsular genes from SV36-T3 to generate the recombinant SV35-T3* which was as virulent as the parental strain SV36-T3* in the murine model and the type 3 capsule was the major virulence factor in the chinchilla model as well. On the other hand, a careful comparison of strains SV36-T3 and the laboratory constructed SV35-T3* in the chinchilla model suggested that some additional determinants present in SV36 but not in the laboratory recombinant may also contribute to the progression of middle ear disease. The nature of this determinants remains to be identified.
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Details
- Title
- In vivo capsular switch in Streptococcus pneumoniae--analysis by whole genome sequencing
- Creators
- Fen Z Hu - Center for Genomic Sciences, Allegheny Singer Research Institute, Pittsburgh, Pennsylvania, United States of AmericaRory EutseyAzad AhmedNelson FrazaoEvan PowellN Luisa HillerTodd HillmanFarrel J BuchinskyRobert BoissyBenjamin JantoJennifer Kress-BennettMark LongwellSuzanne EzzoJ Christopher PostMirjana NesinAlexander TomaszGarth D Ehrlich
- Publication Details
- PloS one, v 7(11), pp e47983-e47983
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- R01 AI080935 / NIAID NIH HHS C76HF03009 / PHS HHS R01 DC005659 / NIDCD NIH HHS DC02148 / NIDCD NIH HHS C76HF09819 / PHS HHS R01 DC004173 / NIDCD NIH HHS 1R01AI080935-01A1 / NIAID NIH HHS R01 DC002148 / NIDCD NIH HHS DC04173 / NIDCD NIH HHS DC05659 / NIDCD NIH HHS SFRH/BD/30103/2006 / FDA HHS C76HF00659 / PHS HHS AI080935 / NIAID NIH HHS DC02148 S1 / NIDCD NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Otolaryngology (and Head and Neck Surgery)
- Web of Science ID
- WOS:000312269500013
- Scopus ID
- 2-s2.0-84869077209
- Other Identifier
- 991014878098204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Infectious Diseases