Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-01-27
2003-08-26
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
06610836
ABSTRACT:
BACKGROUND OF THE INVENTION
The genus Klebsiella belongs to the family Enterobacteriaceae and is divided into at least 4 species. They are gram-negative, capsulated, oxidase-negative, non-motile, straight rods. They are facultative anaerobes, having both a respiratory and fermnentative metabolism. Most strains can use citrate and glucose as their sole carbon source. Some strains can fix nitrogen. They are commonly found in the intestines, clinical samples, soil, water and grains. The species
Klebsiella pneumoniae
can be divided into 3 subspecies;
pneumoniae, ozaenae
and
rhinoscleromatis
(Orskov, I. 1984. Genus V. Klebsiella Trevisan 1885, 105. Krieg and Holt (editors) In Bergey's Manual of Systematic Bacteriology, 1:461-465).
Klebsiella pneumoniae
is the most common gram-negative pathogen causing community acquired pneumonia (Carpenter, J., et al, 1990. Rev Infect. Dis. 12:672-682). Klebsiella is also responsible for an estimated 8% of all nosocomial infections (Sahly, H. and Podschun, R., 1997. Clin. Diagn. Lab. Immunol. 4:393-399).
K. pneumoniae
is an opportunistic pathogen that is associated with pneumonia, septicemia, meningitis, endocarditis, ventriculitis, and infections of urinary tract and wounds. These diseases are both nosocomial and community acquired.
K. pneumoniae
also plays a large role in two major nonrheumatoid arthritic diseases, Ankylosing Spondylitis and Reiter's Syndrome (Schwimmbeck, P. and Oldstone, M., 1989. Current Topics in Microbiology and Immunology. 145:45-56.). Despite available antibiotics, observed mortality rates for pneumonia are approximately 50%, but when bacteremic
K. pneumoniae
occurs in alcoholics, the mortality rises to almost 100% (Sahly, H. and Podschun, R., 1997. Clin. Diagn. Lab. Immunol. 4:393-399). The overall mortality rate for Klebsiella bacteremia in one study was 37% and has ranged in others from 25% to 55% (Watanakunakron, C. and Jura, J., 1991. Scand. J. Infect. Dis. 23:399-405).
Incidence of
K. pneumoniae
meningitis is on the rise. A study of 3377 cases of Bacterial meningitis in 1948, found only 7 were
K. pneumoniae
. In 1957
, K. pneumoniae
accounted for 1.5% of all cases of meningitis. In an eleven-year study, from 1981 to 1991, 13% of culture proven bacterial meningitis cases were
K. pneumoniae
. There was an increase occurrence of
K. pneumoniae
meningitis within this study with 7% occurrence in the first 6 years, and 16% occurrence in the last 5 years (Tang, L-M and Chen, S-T., 1994. Scand. J. Infect. Dis. 26:95-102).
In recent years, Klebsiella strains have become multi-resistant to many antibiotics. In the 1970's, the resistance was mainly to aminoglycoside antibiotics. Since 1982, some Klebsiella strains have become resistant to the extended-spectrum cephalosporins (Sahly, H. and Podschun, R., 1997. Clin. Diagn. Lab. Immunol. 4:393-399). Resistance to the extended-spectrum cephalosporins among clinical isolates of Klebsiella in France and England has been reported at 14 to 16% (Sirot, D. 1995 J. Antimicrob. Chemother. 36:19-34). Since Klebsiella is a good recipient for R factors, resistance has been gained to &bgr;-lactams, tetracycline, chloramphenicols, ceftazidime, sulfonamides and trimethoprim. Today, almost all strains of Klebsiella are resistant to ampicillin. (Orskov, I. 1984. Genus V. Klebsiella Trevisan 1885, 105. Krieg and Holt (editors) In Bergey's Manual of Systematic Bacteriology, 1:461-465).
Microbial fermentation is an important way to convert renewable resources to products of biological and industrial importance.
K. pneumoniae
has been used to convert simple sugars to the commodity chemicals 1,3-propanediol and 1,2-propanediol. These products have been made by fed-batch fermentation of glycerol by
K. pneumoniae
. (Cameron, D. et al, 1998. Biotechnol. Prog. 14:116-125). Genes from the 1,3-propanediol pathway of
K. pneumoniae
have recently been cloned and expressed into both
E. coli
and
S. cerevisiae
. Metabolic engineering of these genes can significantly improve the product yield and productivity (Cameron, D. et al, 1998. Biotechnol. Prog. 14:116-125).
With
K. pneumoniae
playing the lead role, the Klebsiella genus is becoming an increasingly important pathogen. Over the past 10 years, discovery of multi-drug resistant strains has emphasized the importance of this genus. Furthermore, Klebsiella is considered to be a model for systemic infections caused by capsulated bacteria.
SUMMARY OF THE INVENTION
The present invention fulfills the need for diagnostic tools and therapeutics by providing bacterial-specific compositions and methods for detecting Klebsiella species including
K. pneumoniae
, as well as compositions and methods useful for treating and preventing Klebsiella infection, in particular,
K. pneumoniae
infection, in vertebrates including mammals.
The present invention encompasses isolated nucleic acids and polypeptides derived from
K. pneumoniae
that are useful as reagents for diagnosis of bacterial disease, components of effective antibacterial vaccines, and/or as targets for antibacterial drugs including anti-
K. pneumoniae
drugs. They can also be used to detect the presence of
K. pneumoniae
and other Klebsiella species in a sample; and in screening compounds for the ability to interfere with the
K. pneumoniae
life cycle or to inhibit
K. pneumoniae
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
K. pneumoniae
proteins (SEQ ID NO: 1-SEQ ID NO: 7171), including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from
K. pneumoniae
proteins to block protein translation, and methods for producing
K. pneumoniae
proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect
K. pneumoniae
infection. In addition, vaccine compositions and methods for the protection or treatment of infection by
K. pneumoniae
are within the scope of this invention.
In another aspect, the invention relates to the nucliec acids corresponding to 2 naturally occurring plasmids of
K. pneumoniae
; one megaplasmid (SEQ ID NO: 3961-SEQ ID NO: 4368 and SEQ ID NO: 5441-SEQ ID NO: 5445) and the corresponding amino acid sequences (SEQ ID NO: 11132-SEQ ID NO: 11539 and SEQ ID NO: 12612-SEQ ID NO: 12616) and another plasmid (SEQ ID NO: 4637-SEQ ID NO: 4661) and the corresponding amino acid sequences (SEQ ID NO: 11808-SEQ ID NO: 11832).
The nucleotide sequences provided in SEQ ID NO: 1-SEQ ID NO: 7171, 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: 7171 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: 7171, 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: 7171. 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 readab
Breton Gary L.
Osborne Mark
Genome Therapeutics Corporation
Genome Therapeutics Corporation
Woodward Michael P.
Zhou Shubo
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