Prokaryotic polynucleotides polypeptides and their uses

Details Prokaryotic polynucleotides polypeptides and their uses Prokaryotic polynucleotides polypeptides and their uses

1997-09-23

2002-02-19

Davenport, Avis M. (Department: 1600)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S022100, C435S069100, C435S252300, C435S320100, C530S350000, C514S002600, C514S021800, C424S185100

Reexamination Certificate

active

06348582

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides set forth in the Sequence Listing.
BACKGROUND OF THE INVENTION
The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues.
Stapylococcus aureus
(herein “
S. aureus
”) is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome.
While certain Staphylococcal proteins associated with pathogenicity have been identified, e.g., coagulase, hemolysins, leucocidins and exo and enterotoxins, very little is known concerning the temporal expression of such genes during infection and disease progression in a mammalian host. Discovering the sets of genes the bacterium is likely to be expressing at the different stages of infection, particularly when an infection is established, provides critical information for the screening and characterization of novel antibacterials which can interrupt pathogenesis. In addition to providing a fuller understanding of known proteins, such an approach will identify previously unrecognised targets.
GUG is used as an imitating nucleotide, rather than ATG, for a significant number of mRNA's in both Gram positive and Gram negative bacteria. Statistics on the frequency of NTG codons in the start codon for several bacterial species are available on line via computer (http://biochem.otago.ac.nz:800/Transterm/home_page.html).
A discussion of initiation codons in B. subtilis is set forth in Vellanoweth,
RL.1993 in
Bacillus subtilis and other Gram Positive Bacteria, Biochemistry, Physiology and Molecular Genetics,
Sonenshein, Hoch, Losick Eds. Amer. Soc. Microbiol, Washington D.C. p. 699-711. Vellenworth indicates a major difference between
B. subtilis
and the gram-negative organisms is in the choice of initiation codon. 91% of the sequenced
E. coli
genes start with AUG. By contrast, about 30% of
B. subtilis
and other clostridial branch gened start with UUG or GUG. Moreover, CUG functions as a start codon in
B. subtilis.
Mutations of an AUG initiation codon to GUG or UUG often cause decreased expression in
B. subtilis
and
E. coli.
Generally, translation efficiency is higher with AUG initiation codons. A strong Shine-Delgarno ribosome binding site, however, can compensate almost fully for a weak initiation codon. It has been reported that genes with a range of expression levels have initiation codons other than ATG in gram positives (Vellanoweth, RL.1993 in
Bacillus subtilis and other Gram Positive Bacteria, Biochemistry, Physiology and Molecular Genetics,
Sonenshein, Hoch, Losick Eds. Amer. Soc. Microbiol, Washington D.C. p.699-711).
Provided herein are ORF sequences from genes possessing GUG initiation codons and proteins expressed therefrom to be used for screening for antimicrobial compounds. Clearly, there is a need for polypeptide and polynucleotide sequences that may be used to screen for antimicrobial compound and which may also be used to determine the roles of such sequences in pathogenesis of infection, dysfunction and disease. There is also need, therefore, for identification and characterization of such sequences which may play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases.
The polypeptides of the invention have amino acid sequence homology to a known protein(s) as set forth in Table 1.
SUMMARY OF THE INVENTION
It is an object of the invention to provide polypeptides that have been identified as novel polypeptides by homology between an amino acid sequence selected from the group consisting of the sequences set out in the Sequence Listing and a known amino acid sequence or sequences of other proteins such as the protein identities listed in Table 1.
It is a further object of the invention to provide polynucleotides that encode novel polypeptides, particularly polynucleotides that encode polypeptides of
Staphylococcus aureus.
In a particularly preferred embodiment of the invention the polynucleotide comprises a region encoding a polypeptide comprising a sequence sequence selected from the group consisting of the sequences set out in the Sequence Listing, or a variant of any of these sequences.
In another particularly preferred embodiment of the invention there is a novel protein from
Staphylococcus aureus
comprising an amino acid sequence selected from the group consisting of the sequences set out in the Sequence Listing, or a variant of any of these sequences.
In accordance with another aspect of the invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressible by the
Staphylococcus aureus
WCUH29 strain contained in the deposited strain.
A further aspect of the invention there are provided isolated nucleic acid molecules encoding a polypeptide of the invention, particularly
Staphylococcus aureus
polypeptide, and including mRNA, cDNAs, genomic DNAs. Further embodiments of the invention include biologically, diagnostically, prophylactically, clinically or therapeutically useful variants thereof, and compositions comprising the same.
In accordance with another aspect of the invention, there is provided the use of a polynucleotide of the invention for therapeutic or prophylactic purposes, in particular genetic immunization. Among the particularly preferred embodiments of the invention are naturally occurring allelic variants of a polypeptide of the invention and polypeptides encoded thereby.
Another aspect of the invention there are provided novel polypeptides of
Staphylococcus aureus
as well as biologically, diagnostically, prophylactically, clinically or therapeutically useful variants thereof, and compositions comprising the same.
Among the particularly preferred embodiments of the invention are variants of the polypeptides of the invention encoded by naturally occurring alleles of their genes.
In a preferred embodiment of the invention there are provided methods for producing the aforementioned polypeptides.
In accordance with yet another aspect of the invention, there are provided inhibitors to such polypeptides, useful as antibacterial agents, including, for example, antibodies.
In accordance with certain preferred embodiments of the invention, there are provided products, compositions and methods for assessing expression of the polypeptides and polynucleotides of the invention, treating disease, for example, infections of the upper respiratory tract (e.g., otitis media, bacterial tracheitis, acute epiglottitis, thyroiditis), lower respiratory (e.g., empyema, lung abscess), cardiac (e.g., infective endocarditis), gastrointestinal (e.g., secretory diarrhoea, splenic absces, retroperitoneal abscess), CNS (e.g., cerebral abscess), eye (e.g., blepharitis, conjunctivitis, keratitis, endophthalmitis, preseptal and orbital cellulitis, darcryocystitis), kidney and urinary tract (e.g., epididymitis, intrarenal and perinephric absces, toxic shock syndrome), skin (e.g., impetigo, folliculitis, cutaneous abscesses, cellulitis, wound infection, bacterial myositis) bone and joint (e.g., septic arthritis, osteomyelitis), assaying genetic variation, and administering a polypeptide or polynucleotide of the invention to an organism to raise an immunological response against a bacteria, especially a
Staphylococcus aureus

Affiliated with

Also associated with

Rating

Prokaryotic polynucleotides polypeptides and their uses does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Prokaryotic polynucleotides polypeptides and their uses, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Prokaryotic polynucleotides polypeptides and their uses will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2951320