Histidine kinase, 636 HK, of staphylococcus aureus

Details Histidine kinase, 636 HK, of staphylococcus aureus Histidine kinase, 636 HK, of staphylococcus aureus

1999-05-12

2001-02-27

Priebe, Scott D. (Department: 1632)

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

C435S455000, C435S471000, C435S325000, C435S252300, C435S257100, C435S320100, C536S023100, C536S023200, C536S023400, C536S023700

Reexamination Certificate

active

06194174

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 polynucleotides and polypeptides of the Two Component Signal Transduction Histidine Kinase family, as well as their variants, herein referred to as “636 HK,” “636 HK polynucleotide(s),” and “636 HK polypeptide(s)” as the case may be.
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 that are resistant to some or all of the standard antibiotics. This phenomenon has created an unmet medical need and demand for new anti-microbial agents, vaccines, drug screening methods, and diagnostic tests for this organism.
Moreover, the drug discovery process is currently undergoing a fundamental revolution as it embraces “functional genomics,” that is, high throughput genome- or gene-based biology. This approach is rapidly superseding earlier approaches based on “positional cloning” and other methods. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available as well as from other sources. There is a continuing and significant need to identify and characterize further genes and other polynucleotides sequences and their related polypeptides, as targets for drug discovery.
Clearly, there exists a need for polynucleotides and polypeptides, such as the 636 HK embodiments of the invention, that have a present benefit of, among other things, being useful to screen compounds for antimicrobial 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.
SUMMARY OF THE INVENTION
The present invention relates to 636 HK, in particular 636 HK polypeptides and 636 HK polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including treatment of microbial diseases, amongst others. In a firther aspect, the invention relates to methods for identifying agonists and antagonists using the materials provided by the invention, and for treating microbial infections and conditions associated with such infections with the identified agonist or antagonist compounds. In a still further aspect, the invention relates to diagnostic assays for detecting diseases associated with microbial infections and conditions associated with such infections, such as assays for detecting 636 HK expression or activity.
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 636 HK polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a 636 HK of
Staphylococcus aureus
, that is related by amino acid sequence homology to YycG polypeptide. The natural cognate response regulator to the 636 HK histidine kinase of the invention is disclosed in U.S. patent application Ser. No. 09/286,024, filed Apr. 5, 1999. The invention relates especially to 636 HK having a nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO:1 and SEQ ID NO:2 respectively. Note that sequences recited in the Sequence Listing below as “DNA” represent an exemplification of the invention, since those of ordinary skill will recognize that such sequences can be usefully employed in polynucleotides in general, including ribopolynucleotides.
TABLE 1
636 HK Polynucleotide and Polypeptide Sequences
(A)
Staphylococcus aureus
636 HK
polynucleotide sequence [SEQ ID NO:1].
5′-
ATGAAGTGGCTAAAACAACTACAATCCCTTCATACTAAACTTGTAATTGT
TTATGTATTACTGATTATCATTGGTATGCA

AATTATCGGGCTGTATTTTACAAATAATCTTGAAAAAGAGCTGCTTGATA
ATTTTAAGAAGAATATTACGCAGTACGCTA

AACAATTAGAAATTAGTATTGAAAAAGTATATGACGAAAAGGGCTCCGTA
AATGCACAAAAAGATATTCAAAATTTATTA

AGTGAGTATGCCAACCGTCAAGAAATTGGAGAAATTCGTTTTATAGATAA
AGACCAAATTATTATTGCGACGACGAAGCA

GTCTAACCGTAGTCTAATCAATCAAAAAGCGAATGATAGTTCTGTCCAAA
AAGCACTATCACTAGGACAATCAAACGATC

ATTTAATTTTAAAAGATTATGGCGGTGGTAAGGACCGTGTCTGGGTATAT
AATATCCCAGTTAAAGTCGATAAAAAGGTA

ATTGGTAATATTTATATCGAATCAAAAATTAATGACGTTTATAACCAATT
AAATAATATAAATCAAATATTCATTGTTGG

TACAGCTATTTCATTATTAATCACAGTCATCCTAGGATTCTTTATAGCGC
GAACGATTACCAAACCAATCACCGATATGC

GTAACCAGACGGTCGAAATGTCCAGAGGTAACTATACGCAACGTGTGAAG
ATTTATGGTAATGATGAAATTGGCGAATTA

GCTTTAGCATTTAATAACTTGTCTAAACGTGTACAAGAAGCGCAGGCTAA
TACTGAAAGTGAGAAACGTAGACTGGACTC

AGTTATCACCCATATGAGTGATGGTATTATCGCAACAGACCGTCGTGGAC
GTATTCGTATCGTCAATGATATGGCACTCA

AGATGCTTGGTAT&GCGAAAGAAGACATCATCGGATATTACATGTTAAGT
GTATTAAGTCTTGAAGATGAATTTAAACTT

GAAGAAATTCAAGAGAATAATGATAGTTTCTTATTAGATTTAAATGAAGA
AGAAGGTCTAATCGCACGTGTTAACTTTAG

TACGATTGTGCAGGAAACAGGATTTGTAACTGGTTATATCGCTGTGTTAC
ATGACGTTACTGAACAACAACAAGTTGAAC

GTGAGCGTCGTGAATTTGTTGCCAATGTATCACATGAGTTACGTACACCT
TTAACTTCTATGAATAGTTACATTGAAGCA

CTTGAAGAAGGTGCATGGAAAGATGAGGAACTTGCGCCACAATTTTTATC
TGTTACCCGTGAAGAAACAGAACGAATGAT

TCGACTGGTCAATGACTTGCTACAGTTATCTAAAATGGATAATGAGTCTG
ATCAAATCAACAAAGAAATTATCGACTTTA

ACATGTTCATTAATAAAATTATTAATCGACATGAAATGTCTGCGAAAGAT
ACAACATTTATTCGAGATATTCCGAAAAAG

ACGATTTTCACAGAATTTGATCCTGATAAAATGACGCAAGTATTTGATAA
TGTCATTACAAATGCGATGAAATATTCTAG

AGGCGATAAACGTGTCGAGTTCCACGTGAAACAAAATCCACTTTATAATC
GAATGACGATTCGTATTAAAGATAATGGCA

TCGGTATTCCTATCAATAAAGTCGATAAGATATTCGACCGATTCTATCGT
GTAGATAAGGCACGTACGCGTAAAATGGGT

GGTACTGGATTAGGACTAGCCATTTCGAAAGAGATTGTGGAAGCGCACAA
TGGTCGTATTTGGGCAAACAGTGTAGAAGG

TCAAGGTACATCTATCTTTATCACACTTCCATGTGAAGTCATTGAAGACG
GTGATTGGGATGAATAA-3′
(B)
Staphylococcus aureus
636 HK
polypeptide sequence deduced from a polynucleotide
sequence in this table [SEQ ID NO:2].
NH
2
-
MKWLKQLQSLHTKLVIVYVLLIIIGMQIIGLYFTNNLEKELLDNFKKNIT
QYAKQLEISIEKVYDEKGSVNAQKDIQNLL

SEYANRQEIGEIRFIDKDQIIIATTKQSNRSLINQKANDSSVQKALSLGQ
SNDHLILKDYGGGKDRVWVYNIPVKVDKKV

IGNIYIESKINDVYNQLNNINQIFIVGTAISLLITVILGFFIARTITKPI
TDMRNQTVEMSRGNYTQRVKIYGNDEIGEL

ALAFNNLSKRVQEAQANTESEKRRLDSVITHMSDGIIATDRRGRIRIVND
MALKMLGMAKEDIIGYYMLSVLSLEDEFKL

EEIQENNDSFLLDLNEEEGLIARVNFSTIVQETGFVTGYIAVLHDVTEQQ
QVERERREFVANVSHELRTPLTSMNSYIEA

LEEGAWKDEELAPQFLSVTREETERMIRLVNDLLQLSKMDNESDQINKEI
IDFNMFINKIINRHEMSAKDTTFIRDIPKK

TIFTEFDPDKMTQVFDNVITNAMKYSRGDKRVEFHVKQNPLYNRMTIRIK
DNGIGIPINKVDKIFDRFYRVDKARTRKMG

GTGLGLAISKEIVEAHNGRIWANSVEGQGTSIFITLPCEVIEDGDWDE-
COOH
Deposited Materials
A deposit comprising a
Staphylococcus aureus
WCUH 29 strain has been dep

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