Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis

J. E. Adamou, J. H. Heinrichs, A. L. Erwin, W. Walsh, T. Gayle, M. Dormitzer, R. Dagan, Y. A. Brewah, P. Barren, R. Lathigra, S. Langermann, S. Koenig, S. Johnson

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


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.

Original languageEnglish
Pages (from-to)949-958
Number of pages10
JournalInfection and Immunity
Issue number2
StatePublished - 12 Feb 2001
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


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