MecB

Details MecB MecB

2000-07-24

2002-02-12

Devi, S. (Department: 1645)

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

C530S825000, C530S820000, C424S190100, C424S192100, C424S185100, C424S184100, C424S237100, C424S234100, C514S002600

Reexamination Certificate

active

06346608

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, the invention relates to novel polynucleotides and polypeptides of the ClpC ATPase family, hereinafter referred to as “mecB”.
BACKGROUND OF THE INVENTION
It is particularly preferred to employ Staphylococcal genes and gene products as targets for the development of antibiotics. 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.
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.
The frequency of
Staphylococcus aureus
infections has risen dramatically in the past few decades. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate
Staphylococcus aureus
strains which are resistant to some or all of the standard antibiotics. This phenomenon has created a demand for both new anti-microbial agents, vaccines, and diagnostic tests for this organism.
Clearly, there exists a need for factors, such as the mecB embodiments of the invention, that have a present benefit of being useful to screen compounds for antibiotic activity. Such factors are also useful to determine their role in pathogenesis of infection, dysfunction and disease. There is also a need for identification and characterization of such factors and their antagonists and agonists to find ways to prevent, ameliorate or correct such infection, dysfunction and disease.
Certain of the polypeptides of the invention possess amino acid sequence homology to a known ClpC protein.
SUMMARY OF THE INVENTION
It is an object of the invention to provide polypeptides that have been identified as novel mecB polypeptides by homology between the amino acid sequence set out in Table 1 [SEQ ID NO: 2 or 4] and a known amino acid sequence or sequences of other proteins such as ClpC protein.
It is a further object of the invention to provide polynucleotides that encode mecB polypeptides, particularly polynucleotides that encode the polypeptide herein designated mecB.
In a particularly preferred embodiment of the invention the polynucleotide comprises a region encoding mecB polypeptides comprising a sequence set out in Table 1 [SEQ ID NO: 1 or 3] which includes a full length gene, or a variant thereof.
In another particularly preferred embodiment of the invention there is a novel mecB protein from
Staphylococcus aureus
comprising the amino acid sequence of Table 1 [SEQ ID NO: 2 or 4], or a variant thereof.
A further aspect of the invention there are provided isolated nucleic acid molecules encoding mecB, particularly
Staphylococcus aureus
mecB, including mRNAs, 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 mecB and polypeptides encoded thereby.
Another aspect of the invention there are provided novel polypeptides of
Staphylococcus aureus
referred to herein as mecB 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 mecB polypeptide encoded by naturally occurring alleles of the mecB gene.
In a preferred embodiment of the invention there are provided methods for producing the aforementioned mecB 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 mecB expression, treating disease, assaying genetic variation, and administering a mecB polypeptide or polynucleotide to an organism to raise an immunological response against a bacteria, especially a
Staphylococcus aureus
bacteria.
In accordance with certain preferred embodiments of this and other aspects of the invention there are provided polynucleotides that hybridize to mecB polynucleotide sequences, particularly under stringent conditions.
In certain preferred embodiments of the invention there are provided antibodies against mecB polypeptides.
In other embodiments of the invention there are provided methods for identifying compounds which bind to or otherwise interact with and inhibit or activate an activity of a polypeptide or polynucleotide of the invention comprising: contacting a polypeptide or polynucleotide of the invention with a compound to be screened under conditions to permit binding to or other interaction between the compound and the polypeptide or polynucleotide to assess the binding to or other interaction with the compound, such binding or interaction being associated with a second component capable of providing a detectable signal in response to the binding or interaction of the polypeptide or polynucleotide with the compound; and determining whether the compound binds to or otherwise interacts with and activates or inhibits an activity of the polypeptide or polynucleotide by detecting the presence or absence of a signal generated from the binding or interaction of the compound with the polypeptide or polynucleotide.
In accordance with yet another aspect of the invention, there are provided mecB agonists and antagonists, preferably bacteriostatic or bacteriocidal agonists and antagonists.
In a further aspect of the invention there are provided compositions comprising a mecB polynucleotide or a mecB polypeptide for administration to a cell or to a multicellular organism.
Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following descriptions and from reading the other parts of the present disclosure.
DESCRIPTION OF THE INVENTION
The invention relates to novel mecB polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a novel mecB of
Staphylococcus aureus
, which is related by amino acid sequence homology to ClpC polypeptide. The invention relates especially to mecB having the nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO: 1 and SEQ ID NO: 2 respectively.
TABLE 1
mecB Polynucleotide and Polypeptide Sequences
(A) Sequences from
Staphylococcus aureus
mecB polynucleotide
sequence [SEQ ID NO:1].
5′-
1
ATGTTATTTG GTAGATTAAC TGAACGTGCA CAGCGCGTAT TAGCACATGC

51
ACAAGAAGAA GCAATTCGTT TAAATCATTC TAATATAGGA ACAGAACACC

101
TATTATTGGG GTTAATGAAA GAACCTGAAG GAATTGCTGC AAAAGTATTA

151
GAAAGTTTTA ATATCACTGA AGATAAAGTA ATTGAAGAAG TTGAAAAATT

201
AATCGGACAT GGTCAAGATC ATGTTGGTAC ATTGCATTAT ACACCTAGAG

251
CTAAAAAAGT CATTGAATTA TCGATGGATG AAGCTAGAAA ATTACATCAC

301
AATTTTGTTG GAACGGTTCA TCTTTTATTA GGCTTGATTC GTGAAAATGA

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