Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-04-05
2003-08-12
Woodward, Michael P. (Department: 1631)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S024100, C435S006120, C435S320100, C435S325000
Reexamination Certificate
active
06605709
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to isolated nucleic acids and polypeptides derived from
Proteus mirabilis
that are useful as molecular targets for diagnostics, prophylaxis and treatment of pathological conditions, as well as materials and methods for the diagnosis, prevention, and amelioration of pathological conditions resulting from bacterial infection.
BACKGROUND OF THE INVENTION
The genus Proteus is a member of the family Enterobacteriaceae, They are Gram-negative, facultatively anaerobic, straight rods. The species are motile by peritrichous flagella. The genus contains at least 3 species that are often isolated from the intestines of humans and animals, manure, soil, and polluted waters. The genus was first described in 1885 by Hauser (Penner, J. 1984. Genus XI. Proteus Hauser 1885, 12. Krieg and Holt (editors) In Bergey's Manual of Systematic Bacteriology, 1:491-494).
Proteus mirabilis
can differentiate from short vegetative swimmer cells to elongated, highly flagellated, multicellular, swarmer cells. These changes are in response to growth on surfaces or in viscous environments. (Mobley, H., et al, 1995. Trends Microbiol. 3:280-284.). The swarmer cells have been implicated in the migration of
P. mirabilis
to the kidneys, where invasion of the of the renal tissue can occur (Allison, C., 1994. J. Infect. Dis. 169:1155-1158.).
P. mirabilis
is the most common member of this genus to be isolated from clinical specimens. Bacteremia caused by
P. mirabilis
is often difficult to treat and mortality rates range from 15% to 88% depending on the severity of the underlying disease. It is most often associated with urinary tract infections (UTI), especially in patients with indwelling catheters, and is second only to
E. coli
in prevalence (Senior, B., 1997. J. Med. Microbiol. 46:407-412). A major complication of long-term urethral catheterization is the encrustation of the catheter by biofilms from bacteria that include
P. mirabilis
(Stickler, D., 1993. Urol. Res. 21:407-411.). The infection usually starts in the bladder, causing bacteriuria and cystitis. It then spreads to the kidneys, where it can cause acute pyelonephritis, chronic inflammation, periurethral abscesses, renal failure, and bacteremia. An inducible urease can cause stone formation in the bladder and kidneys. (Oelschlaeger, T., 1996. Microbial Pathogenesis. 21:1-16.). Other virulence factors include hemolysin, fimbriae, amino acid deaminase, and an imunoglobulin-A-degrading protease. The expression of many of these virulence factors are regulated by the differentiation of the swarmer cell (Mobley, H., et al, 1995. Trends Microbiol. 3:280-284). Although less common,
P. mirabilis
has also been isolated from infections of wounds, burns, respiratory tract, eyes, ears and throat.
While there is still excellent activity of many antibiotics, there has been an increase in antibiotic resistance by
P. mirabilis
. Plasmid-mediated transfer of antibiotic resistance genes has been partially responsible for this increase. Wild-type strains of
P. mirabilis
are susceptible to all penicillins and cephalosporins. (Bret, L., et al, 1998. Antimicrob. Agents Chemother. 42:1110-1114.). The first extended-spectrum &bgr;-lactamases were discovered in 1991 (Wantanabe, Y., et al, 1991. Microbiol. Immunol.35:87-97.). With the acquisition of TEM and TEM-derived &bgr;-lactamases, strains can be found resistance to any or most of the &bgr;-lactam antibiotics (Mariotte, S., et al, 1994. J. Antimicrobial Chemotherapy. 33:925-935.). Strains have even been found that are resistant to imipenem, which has the widest antibacterial spectrum of currently available &bgr;-lactam antibiotics (Neuwirth, C., et al, 1995. J. Antimicrobial Chemotherapy. 36:335-342.).
Sequencing and further analysis of this genome will aid in the identification of essential genes for development of drug targets and reduce the emerging health threat this organism poses.
SUMMARY OF THE INVENTION
The present invention fulfills the need for diagnostic tools and therapeutics by roviding bacterial-specific compositions and methods for detecting Proteus speciesincluding
P. mirabilis
, as well as compositions and methods useful for treating and preventing Proteus infection, in particular,
P. mirabilis
infection, in vertebrates including mammals.
The present invention encompasses isolated nucleic acids and polypeptides derived from
P. mirabilis
that are useful as reagents for diagnosis of bacterial disease, components of effective antibacterial vaccines, and/or as targets for antibacterial drugs including anti-
P. mirabilis
drugs. They can also be used to detect the presence of
P. mirabilis
and other Proteus species in a sample; and in screening compounds for the ability to interfere with the
P. mirabilis
life cycle or to inhibit
P. mirabilis
infection. They also have use as biocontrol agents for plants.
In one aspect, the invention features compositions of nucleic acids corresponding to entire coding sequences of
P. mirabilis
proteins, including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from
P. mirabilis
proteins to block protein translation, and methods for producing
P. mirabilis
proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect
P. mirabilis
infection. In addition, vaccine compositions and methods for the protection or treatment of infection by
P. mirabilis
are within the scope of this invention.
The nucleotide sequences provided in SEQ ID NO: 1-SEQ ID NO: 4172, a fragment thereof, or a nucleotide sequence at least about 99.5% identical to a sequence contained within SEQ ID NO: 1-SEQ ID NO: 4172 may be “provided” in a variety of medias to facilitate use thereof. As used herein, “provided” refers to a manufacture, other than an isolated nucleic acid molecule, which contains a nucleotide sequence of the present invention, i.e., the nucleotide sequence provided in SEQ ID NO: 1-SEQ ID NO: 4172, a fragment thereof, or a nucleotide sequence at least about 99.5% identical to a sequence contained within SEQ ID NO: 1-SEQ ID NO: 4172. Uses for and methods for providing nucleotide sequences in a variety of media is well known in the art (see e.g., EPO Publication No. EP 0 756 006).
In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, “computer readable media” refers to any media which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage media, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A person skilled in the art can readily appreciate how any of the presently known computer readable media can be used to create a manufacture comprising computer readable media having recorded thereon a nucleotide sequence of the present invention.
As used herein, “recorded” refers to a process for storing information on computer readable media. A person skilled in the art can readily adopt any of the presently known methods for recording information on computer readable media to generate manufactures comprising the nucleotide sequence information of the present invention.
A variety of data storage structures are available to a person skilled in the art for creating a computer readable media having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable media. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordP
Genome Therapeutics Corporation
Genome Therapeutics Corporation
Woodward Michael P.
Zhou Shubo
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