Genes and proteins and their use

Details Genes and proteins and their use Genes and proteins and their use

2001-09-10

2004-11-02

Smith, Lynette R. F. (Department: 1645)

Chemistry: molecular biology and microbiology

Micro-organism, per se ; compositions thereof; proces of...

Bacteria or actinomycetales; media therefor

C435S069100, C435S252330, C435S252400, C435S320100, C424S190100, C536S023700

Reexamination Certificate

active

06812021

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to the identification of bacterial genes and proteins, and their use. More particularly, it relates to their use in therapy, for immunisation and in screening for drugs.
BACKGROUND TO THE INVENTION
Group B Streptococcus (GBS), also known as
Streptococcus agalactiae
, is the causative agent of various conditions. In particular, GBS causes:
Early Onset Neonatal Infection.
This infection usually begins in utero and causes severe septicaemia and pneumonia in infants, which is lethal if untreated and even with treatment is associated with a 10-20% mortality rate.
Late Onset Neonatal Infection.
This infection occurs in the period shortly after birth until about 3 months of age. It causes a septicaemia, which is complicated by meningitis in 90% of cases. Other focal infections also occur including osteomyelitis, septic arthritis, abscesses and endopthalmitis.
Adult Infections.
These appear to be increasingly common and occur most frequently in women who have just delivered a baby, the elderly and the immunocompromised. They are characterised by septicaemia and focal infections including osteomyelitis, septic arthritis, abscesses and endopthalmitis.
Urinary Tract Infections.
GBS is a cause of urinary tract infections and in pregnancy accounts for about 10% of all infections.
Veterinary Infections.
GBS causes chronic mastitis in cows. This, in turn, leads to reduced milk production and is therefore of considerable economic importance.
GBS infections can be treated with antibiotics. However, immunisation is preferable. It is therefore desirable to develop an immunogen that could be used in a therapeutically-effective vaccine.
SUMMARY OF THE INVENTION
The present invention is based on the identification of a series of genes in GBS, and also related organisms, the products of which may be localised on the outer surface of the organism and therefore may be used as a target for immuno-therapy.
According to one aspect of the invention, a peptide is encoded by an operon including any of the genes identified herein as pho1-13, pho3-21, pho2-15, pho3-18, pho3-22, pho3-3, pho3-17, pho2-2, pho1-5, pho3-1, pho3-23, pho3-50, pho1-14, pho2-10, pho3-14, pho3-24 and pho3-29, obtainable from Group B Streptococcus, or a homologue or functional fragment thereof. Such a peptide is suitable for therapeutic use e.g. when isolated.
The term “functional fragments” is used herein to define a part of the gene or peptide which retains the activity of the whole gene or peptide. For example, a functional fragment of the peptide may be used as an antigenic determinant, useful in a vaccine or in the production of antibodies.
A gene fragment may be used to encode the active peptide. Alternatively, the gene fragment may have utility in gene therapy, targetting the wild-type gene in vivo to exert a therapeutic effect.
A peptide according to the present invention may comprise any of the amino acid sequences identified herein as SEQ ID NOS. 2, 4, 6, 8, 10, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33 and 35, or a functional fragment thereof.
Because of the extracellular or cell surface location, the peptides of the present invention may be suitable candidates for the production of therapeutically-effective vaccines against GBS. The term “therapeutically-effective” is intended to include the prophylactic effect of vaccines. For example, a vaccine may comprise a peptide according to the invention, or the means for its expression, for th treatment of infection. The vaccine may be administered to females prior to or during pregnancy to protect mother and neonate against infection by GBS.
According to another aspect of the invention, the peptides or genes may be used for screening potential antimicrobial drugs or for the detection of virulence.
A further aspect of this invention is the use of any of the products identified herein, for the treatment or prevention of a condition associated with infection by a Group B Streptococcal strain.
Although the protein has been described for use in the treatment of patients, veterinary uses of the products of the invention are also considered to be within the scope of the present invention. In particular, the peptides or the vaccines may be used in the treatment of chronic mastitis, especially in cows.


REFERENCES:
patent: 0006736 (1999-07-01), None
Ellis, R.W. (Chapter 29 of “VACCINES” Plotkin, 5.A. et al. (eds) published by W. B. Saunders company (Philadelphia) in 1988,.*
Rudinger et al, in “Peptide Hormones”, edited by Parsons, J.A., University Park Press, Jun. 1976, p. 6.*
Burgess et al., The Journal of Cell Biology, 111:2129-2138, 1990.*
Lazar et al., Molecular and Cellular Biology, 8(3): 1247-1252, 1988.*
Jobling et al. (Mol. Microbiol. 1991, 5(7): 1755-67.*
Larsson, Charlotte, Margaretha St{dot over (a)}hammar-Carlemalm, Gunnar Lindahl (Sep. 1996) “Experimental Vaccination Against Group B Streptococcus, an Encapsulated Bacterium, with Highly Purified Preparations of Cell Surface Proteins Rib and &agr;”Infection and Immunity64(9):3518-3523.
Wastfelt, Maria, Margaretha Stalhammar-Carlemalm, Anne-Marie Delisse et al. (Aug. 1996) “Identification of a Family of Streptococcal Surface Proteins with Extremely Repetitive Structure”The Journal of Biological Chemistry271(31):18892-18897.
Giffard, Philip M., Catherine Rathsam, Edward Kwan et al. (1993) “The ftf gene encoding the cell-bound fructosyltransferase ofStreptococcus salivariusATCC 25975 is preceded by an insertion sequence and followed by FUR1 and clpP homologues”Journal of General Microbiology139:913-920.
Giffard, Philip M. et al. Sequence ID CLPP_STRSL, Jun. 1, 1994, EMBL Database Accession no P36398.
Maurizi, Michael R., William P. Clark, Yoko Katayama et al. (Jul. 1990) “Sequence and Structure of Clp P, the Proteolytic Component of the ATP-dependent Clp Protease ofEscherichia coli”The Journal of Biological Chemistry265(21):12536-12545.
Tsukioka, Yuichi, Yoshihisa Yamashita, Takahiko Oho et al. (Feb. 1997) “Biological Function of the dTDP-Rhamnose Synthesis Pathway inStreptococcus mutans” Journal of Bacteriology179(4):1126-1134.
Yuichi, Tsukioka et al., Sequence ID P95779, May 1, 1997, EMBL Database Accesssion no P95779.
Coffey, T. et al. (Jun. 1998) “Recombinational exchanges at the capsular polysacchairde biosynthesis locus . . . ”Molecular Microbiology27:73-83; EMBL Database Accession No. 054547 Sequence ID 054547. Sequence only.

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