In Vivo Capsular Switch in Streptococcus pneumoniae - Analysis by Whole Genome Sequencing

Fen Z. Hu, Rory Eutsey, Azad Ahmed, Nelson Frazao, Evan Powell, N. Luisa Hiller, Todd Hillman, Farrel J. Buchinsky, Robert Boissy, Benjamin Janto, Jennifer Kress-Bennett, Mark Longwell, Suzanne Ezzo, J. Christopher Post, Mirjana Nesin, Alexander Tomasz, Garth D. Ehrlich

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere47983
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 8 2012

Fingerprint

Streptococcus pneumoniae
Genes
Switches
Genome
genome
Chinchilla
virulence
Capsules
Virulence
genes
Genetic Transformation
Ear Diseases
animal models
Bacteriocins
ear diseases
Nasopharynx
nasopharynx
Pandemics
Virulence Factors
Middle Ear

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Hu, F. Z., Eutsey, R., Ahmed, A., Frazao, N., Powell, E., Hiller, N. L., ... Ehrlich, G. D. (2012). In Vivo Capsular Switch in Streptococcus pneumoniae - Analysis by Whole Genome Sequencing. PloS one, 7(11), [e47983]. https://doi.org/10.1371/journal.pone.0047983

In Vivo Capsular Switch in Streptococcus pneumoniae - Analysis by Whole Genome Sequencing. / Hu, Fen Z.; Eutsey, Rory; Ahmed, Azad; Frazao, Nelson; Powell, Evan; Hiller, N. Luisa; Hillman, Todd; Buchinsky, Farrel J.; Boissy, Robert; Janto, Benjamin; Kress-Bennett, Jennifer; Longwell, Mark; Ezzo, Suzanne; Post, J. Christopher; Nesin, Mirjana; Tomasz, Alexander; Ehrlich, Garth D.

In: PloS one, Vol. 7, No. 11, e47983, 08.11.2012.

Research output: Contribution to journalArticle

Hu, FZ, Eutsey, R, Ahmed, A, Frazao, N, Powell, E, Hiller, NL, Hillman, T, Buchinsky, FJ, Boissy, R, Janto, B, Kress-Bennett, J, Longwell, M, Ezzo, S, Post, JC, Nesin, M, Tomasz, A & Ehrlich, GD 2012, 'In Vivo Capsular Switch in Streptococcus pneumoniae - Analysis by Whole Genome Sequencing', PloS one, vol. 7, no. 11, e47983. https://doi.org/10.1371/journal.pone.0047983
Hu, Fen Z. ; Eutsey, Rory ; Ahmed, Azad ; Frazao, Nelson ; Powell, Evan ; Hiller, N. Luisa ; Hillman, Todd ; Buchinsky, Farrel J. ; Boissy, Robert ; Janto, Benjamin ; Kress-Bennett, Jennifer ; Longwell, Mark ; Ezzo, Suzanne ; Post, J. Christopher ; Nesin, Mirjana ; Tomasz, Alexander ; Ehrlich, Garth D. / In Vivo Capsular Switch in Streptococcus pneumoniae - Analysis by Whole Genome Sequencing. In: PloS one. 2012 ; Vol. 7, No. 11.
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