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

Abstract:

: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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Adamou JE,Heinrichs JH,Erwin AL,Walsh W,Gayle T,Dormitzer M,Dagan R,Brewah YA,Barren P,Lathigra R,Langermann S,Koenig S,Johnson S

doi

10.1128/IAI.69.2.949-958.2001

keywords:

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

949-58

issue

2

eissn

0019-9567

issn

1098-5522

journal_volume

69

pub_type

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