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 language | English (US) |
|---|---|
| Pages (from-to) | 1264-1273 |
| Number of pages | 10 |
| Journal | Journal of Infectious Diseases |
| Volume | 203 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2011 |
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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 journal › Article
}
TY - JOUR
T1 - Designed reduction of Streptococcus pneumoniae pathogenicity via synthetic changes in virulence factor codon-pair bias
AU - Coleman, J. Robert
AU - Papamichail, Dimitris
AU - Yano, Masahide
AU - Del Mar García-Suárez, María
AU - Pirofski, Liise-anne
PY - 2011/5/1
Y1 - 2011/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79954608598&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954608598&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir010
DO - 10.1093/infdis/jir010
M3 - Article
C2 - 21343143
AN - SCOPUS:79954608598
VL - 203
SP - 1264
EP - 1273
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 9
ER -