Designed reduction of Streptococcus pneumoniae pathogenicity via synthetic changes in virulence factor codon-pair bias

J. Robert Coleman, Dimitris Papamichail, Masahide Yano, María Del Mar García-Suárez, Liise-anne Pirofski

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

In this study, we used a previously described method of controlling gene expression with computer-based gene design and de novo DNA synthesis to attenuate the virulence of Streptococcus pneumoniae. We produced 2 S. pneumoniae serotype 3 (SP3) strains in which the pneumolysin gene (ply) was recoded with underrepresented codon pairs while retaining its amino acid sequence and determined their ply expression and pneumolysin production in vitro and their virulence in a mouse pulmonary infection model. Expression of ply and production of pneumolysin of the recoded SP3 strains were decreased, and the recoded SP3 strains were less virulent in mice than the wild-type SP3 strain or a Dply SP3 strain. Further studies showed that the least virulent recoded strain induced a markedly reduced inflammatory response in the lungs compared with the wild-type or Δply strain. These findings suggest that reducing pneumococcal virulence gene expression by altering codon-pair bias could hold promise for rational design of live-attenuated pneumococcal vaccines.

Original languageEnglish (US)
Pages (from-to)1264-1273
Number of pages10
JournalJournal of Infectious Diseases
Volume203
Issue number9
DOIs
StatePublished - May 1 2011

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Virulence Factors
Streptococcus pneumoniae
Codon
Virulence
Gene Expression
Genes
Lung
Pneumococcal Vaccines
Attenuated Vaccines
Streptococcus pneumoniae plY protein
Amino Acid Sequence
Serogroup
DNA
Infection

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Designed reduction of Streptococcus pneumoniae pathogenicity via synthetic changes in virulence factor codon-pair bias. / Coleman, J. Robert; Papamichail, Dimitris; Yano, Masahide; Del Mar García-Suárez, María; Pirofski, Liise-anne.

In: Journal of Infectious Diseases, Vol. 203, No. 9, 01.05.2011, p. 1264-1273.

Research output: Contribution to journalArticle

Coleman, J. Robert ; Papamichail, Dimitris ; Yano, Masahide ; Del Mar García-Suárez, María ; Pirofski, Liise-anne. / Designed reduction of Streptococcus pneumoniae pathogenicity via synthetic changes in virulence factor codon-pair bias. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 9. pp. 1264-1273.
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