Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1998-08-13
2002-04-30
Campbell, Eggerton A. (Department: 1656)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S022100
Reexamination Certificate
active
06380370
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to isolated nucleic acids and polypeptides derived from
Staphylococcus epidermidis
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.
BRIEF DESCRIPTION OF THE SEQUENCE LISTING
Incorporated herein by reference in its entirety is a Sequence Listing, comprising SEQ ID NO: 1 to SEQ ID NO: 5674. The Sequence Listing is contained on a CD-ROM, three copies of which are filed, the Sequence Listing being in a computer-readable ASCII file named “Gtc007.pto”, created on May 15, 2001 and of 9,485,000 bytes in size, in IBM-PC Windows®NT v4.0 format.
BACKGROUND OF THE INVENTION
Staphylococcus epidermidis
(
S. epidermidis
) is a species of staphylococcal bacteria that are Gram-positive, nonmotile, nonpigmented and coagulase-negative cocci, which are mainly found on the skin and mucous membrane of warm-blooded animals. Their large numbers and ubiquitous distribution result in frequent contamination of specimens collected from or through the skin, making these organisms amongst the most frequently isolated in the clinical laboratory. In the past,
S. epidermidis
was rarely the cause of significant infections, but with the increasing use of implanted catheters and prosthetic devices, it has emerged as an important agent of hospital-acquired infections and has been recognized as a true pathogen (Lowy and Hammer, 1983, Ann Intern Med, 99: 834-9; Blum and Rodvold, 1987, Clin Pharm, 6: 464-75; Hamory, Parisi et al., 1987, Am J Infect Control, 15: 59-74).
S. epidermidis
is a major cause of infection of indwelling foreign devices such as, orthopedic devices, intravenous catheters, prosthetic heart valves, central nervous system shunts, and peritoneal dialysis catheters (Blum and Rodvold, 1987, Clin Pharm, 6: 464-75; Archer, 1988, J Antimicrob Chemother, 21 Suppl C: 133-8)(Lowy and Hammer, 1983, Ann Intern Med, 99: 834-9; Hamory, Parisi et al., Staphylococcus 1987. Am J Infect Control, 15: 59-74). In addition
S. epidermidis
is a common cause of postoperative wound infections, bacteremia of immunosuppressed patients, intensive-care unit patients and premature newborns (MacLowry, 1983, Am J Med, 75: 2-6)(Eykyn, 1988, Lancet, 1: 100-4). According to a national survey (Centers for Disease Control, 1981:7)
S. epidermidis
caused 8.9% of primary nosocomial bacteremias.
Treatment of
S. epidermidis
infections remains difficult because of the occult nature, association with foreign bodies, and frequent resistance to antimicrobial agents. Ordinarily,
S. epidermidis
is an organism with low virulence, however breaks in host defense caused by surgery, catheter placement, prosthesis insertion or immunosuppression is prerequisite for infection. The presence of foreign bodies itself facilitates infection by protecting the organism from elimination by host defenses or antimicrobial therapy (Lowy and Hammer, 1983, Ann Intern Med, 99: 834-9). Furthermore,
S. epidermidis
due to its ability to produce extracellular polysaccharide material or slime, may be uniquely adapted to adhere to smooth surfaces such as plastics or metal. Slime producing strains of
S. epidermidis
appear to be more pathogenic than non-slime producing strains (Christensen, Simpson et al., 1983, Infect Immun, 40: 407-10; Peters and Pulverer, 1984, J Antimicrob Chemother, 14 Suppl D: 67-71; Gallimore, Gagnon et al., 1991, J Infect Dis, 164: 1220-3). This property and many factors are involved in the pathogenesis of device associated infections. Despite the increased recognition as a pathogen,
S. epidermidis
infections are difficult to diagnose. Differentiating clinically important from clinically unimportant bacterial isolates of
S. epidermidis
is difficult because of the high rate of contamination.
Although laboratory isolates of
S. epidermidis
have generally been susceptible to semisynthetic penicillins (methicillin, nafcillin, oxacillin), cephalosporins, amino-glycosides, vancomycin and rafampin, recent clinical isolates have had an increased resistance. Recent reports (Karchmer, 1985, Am J Med, 78: 116-27; Karchmer, 1991, J Hosp Infect, 18 Suppl A: 355-66) show that 83% of
S. epidermidis
isolates from patients with prosthetic valve endocarditis are methicillin resistant and 32% are gentamicin resistant as well. Multi-drug resistant staphylococci have emerged in the midst of high level use of penicillin and aminoglycosides (Centers for Disease Control and Prevention, 1993
MMWR
42:597; and S. Handwerger et al., 1993,
Clin Infect Dis
16:750).
The use of antibiotics for therapeutics and prophylactic purposes, promotes the selection of resistant organisms and the spread of antibiotic resistance genes among bacteria. Previous studies have shown that virtually all staphylococci carry some antibiotic resistance genes on naturally occurring extrachromosomal mobile genetic elements, such as the plasmids. Survey and analysis of plasmids in clinical isolates of
S. epidermidis
have shown that more that 80% of isolates carry plasmids and in several cases more than one plasmid (Archer et al., 1982, Infect Immun, 35:627-632; Kloos et al., 1981, Can J Microbiol, 27:271-278; Moller, 1988, J Hosp Infect 12:19-27). Though the most important forms of resistance has been the inactivation of antibiotics, particularly penicillins and cephalosporins, recent clinical isolates have resistance to one or more of the following antibiotics, methicillin, tetracycline, erythromycin, gentamycin, kanamycin and chloramphenicol. In fact due to the wide spread occurrence of plasmids and their involvement in antibiotic resistance, plasmid profiling has been used as an epidemiological reagent to study nosocomial infections. This invention relates to isolated nucleic acids and polypeptides derived from
S. epidermidis
plasmids that are useful as molecular targets for diagnosis, 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.
These concerns point to the need for diagnostic tools and therapeutics aimed at proper identification of strain and eradication of virulence. The design of vaccines that will limit the spread of infection and halt transfer of resistance factors is very desirable.
SUMMARY OF THE INVENTION
The present invention fulfills the need for diagnostic tools and therapeutics by providing bacterial-specific compositions and methods for detecting, treating, and preventing bacterial infection, in particular
S. epidermidis
infection.
The present invention encompasses isolated nucleic acids and polypeptides derived from
S. epidermidis
that are useful as reagents for diagnosis of bacterial disease, components of effective antibacterial vaccines, and/or as targets for antibacterial drugs including anti-
S. epidermidis
drugs. They can also be used to detect the presence of
S. epidermidis
and other Staphylococcus species in a sample; and in screening compounds for the ability to interfere with the
S. epidermidis
life cycle or to inhibit
S. epidermidis
infection. They also has use as biocontrol agents for plants.
More specifically, this invention features compositions of nucleic acids corresponding to entire coding sequences of
S. epidermidis
proteins, including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from
S. epidermidis
proteins to block protein translation, and methods for producing
S. epidermidis
proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect
S. epidermidis
infection. In addition, vaccine compositions and methods for the protection or treatment of infection by
S. epidermidis
are within the scope of this invention.
The nucleotide sequences provided in SEQ ID NO: 1-SEQ ID NO: 2837, a fr
Bush David
Doucette-Stamm Lynn A.
Burns Doane Swecker & Mathis L.L.P.
Campbell Eggerton A.
Genome Therapeutics Corporation
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