TY - JOUR
T1 - Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis
AU - Adamou, J. E.
AU - Heinrichs, J. H.
AU - Erwin, A. L.
AU - Walsh, W.
AU - Gayle, T.
AU - Dormitzer, M.
AU - Dagan, R.
AU - Brewah, Y. A.
AU - Barren, P.
AU - Lathigra, R.
AU - Langermann, S.
AU - Koenig, S.
AU - Johnson, S.
PY - 2001/2/12
Y1 - 2001/2/12
N2 - Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface. Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes.
AB - Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface. Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes.
UR - http://www.scopus.com/inward/record.url?scp=0035143948&partnerID=8YFLogxK
U2 - 10.1128/IAI.69.2.949-958.2001
DO - 10.1128/IAI.69.2.949-958.2001
M3 - Article
C2 - 11159990
AN - SCOPUS:0035143948
SN - 0019-9567
VL - 69
SP - 949
EP - 958
JO - Infection and Immunity
JF - Infection and Immunity
IS - 2
ER -
