Chemistry: molecular biology and microbiology – Vector – per se
Reexamination Certificate
1998-08-13
2003-09-09
Mosher, Mary E. (Department: 1648)
Chemistry: molecular biology and microbiology
Vector, per se
C536S023700, C536S024320, C435S252300, C435S069100, C435S006120
Reexamination Certificate
active
06617156
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to isolated nucleic acids and polypeptides derived from
Enterococcus faecalis
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.
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: 6812. 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 “GTC005.pto”, created on Sep. 6, 2001 and of 10.3 megabytes in size, in Windows NT 4.0, ASCII text format.
BACKGROUND OF THE INVENTION
Enterococcus faecalis
(
E. faecalis
) is a gram-positive, facultative, anaerobic cocci, that is widely distributed in nature, animals, and humans. Enterococci are part of the normal gastrointestinal and genital tract flora, and among the 17 known species,
E. faecalis
is dominant in humans, accounting for 80-90% of clinically isolated specimens, and it exhibits increasing levels of multidrug resistance (Kaufhold, A and Klein, R (1995)
Zentralblatt fuer Bakteriologie
282 (4): 507-518; and Svec, P, Sedlacek, I, and Pakrova, E (1996)
Epidemiologie Mikrobiologie Imunologie
45: 153-157).
E. faecalis
infections include urinary tract infections (UTI), bacteremia, endocarditis, and wound and abdominal-pelvic infections, accounting for 16% of all UTIs, and 8% of all becteremias (Ardino, R C, and Murray, B E (1990) Principles and Practice of Infectious Diseases, 3rd ed., Mandell et al, eds., Update Vol. 2, No. 4).
Vancomycin resistant enterococci (VRE) have emerged in the midst of high level resistance to penicillin and aminoglycosides (Centers for Disease Control and Prevention (1993)
MMWR
42:597-599; and Handwerger, S, et al (1993)
Clin Infect Dis
16:750-755). Resistance can be intrinsic (chromosomally mediated), or acquired (plasmid or transposon mediated), with higher levels of resistance in acquired. VRE are characterized by resistance to virtually all available antibiotics, including vancomycin, considered the “last resort” antibiotic effective against gram-positive bacteria. Treatment options for physicians are limited, with the latest strategy being combinations of antimicrobials or the use of new unproven compounds (Moellering, R C Jr. (1991)
J Antimicrob Chemother
28: 1-12; and Hayden, M K et al (1994)
Antimicrob Agents Chemother
38 1225-1229; and Mobarakai, N et al (1994)
J Antimicrob Chemother
33: 319-321). From 1989 through 1993, the percentage of nosocomial (hospital incurred) infections by VRE increased from 0.3% to 7.9% (Centers for Disease Control and Prevention (1993)
MMWR
42:597-599). There was a 34-fold increase in ICU patients, and a increasing trend among non-ICU patients (Centers for Disease Control and Prevention (1993)
MMWR
42:597-599). These numbers may not be an accurate reflection of the actual total, as clinical identification of vancomycin resistance is not consistently detected, especially in the VanB phenotype which confers moderate resistance (Tenover, F C (
1993)
J Clin Microbiol
31:1695-1699; and Sahm, D F (1990)
Antimicrob Agents Chemother
34: 1846-1848; and Zabransky, R J (1994)
Microbiol Infect Dis
20:113-116). Patients can be colonized and carry VRE without symptoms, with chief areas of colonization being anus, axilla, stool, perineal, umbilicus, wounds, foley catheters, and colostomy sites.
Epidemiology of
E. faecalis
is not completely understood, but it is thought that most infections and colonizations are a result of the patient's endogenous flora (Murray, B E (1990)
Clin Microbiol Rev
3:46-65). Recent evidence suggests that
E. faecalis
can be spread by direct contact with other infected patients, indirect transmission from hospital personnel (Boyce, J M et al (1994)
J Clin Microbiol
32:1148-53; and Rhineheart, E et al (1990)
N Engl J Med
323:1814-1818), or from contaminated hospital surfaces and equipment (Karanfil, L V et al (1992)
Infect Control Hosp Epidemiol
13:195-200; and Boyce, J M et al (1994)
J Clin Microbiol
32:1148-53; and Livornese, L L Jr. (1992)
Ann Intern Med
117:112-116). Increased risk for the critically ill, those with underlying disease of immunosuppression (i.e. ICU, oncology, and transplant patients), cardio-thoracic/intraabdominal surgical patients and those with urinary or central venous catheters has been demonstrated. In addition, risk for
E. faecalis
infection increases for patients with long hospital stays or previous multiantimicrobial or vancomycin treatments (Boyce, J M et al (1994)
J Clin Microbiol
32:1148-1153; Boyle, J F et al (1993)
J Clin Microbiol
31:1280-1285; Karanfil, L V et al (1992)
Infect Control Hosp Epidemiol
13:195-200; Handwerger, S et al (1993)
Clin Infect Dis
16:750-755; Montecalvo, M A et al (1994)
Antimicrob Agents Chemother
38:1363-1367).
Additional concern stems from the ability of the
E. faecalis
plasmid borne VanA gene, which confers high level vancomycin resistance, to transfer in vitro to several gram positive microorganisms such as
Staphylococcus aureus
(Leclercq, R et al (1989)
Antimicrob Agents Chemother
33:10-15; and Noble, W C, et al (1992)
FEMS Microbiology Letters
72:195-198). To date, no clinical isolates of
S. aureus
or
S. epidermidis
have shown vancomycin resistance conferred by plasmid transfer, but clinically isolated strains of
S. haemolyticus
have (Degner, J E, et al (1994)
J Clin Microbiol
32:2260-2265; and Veach, L A, et al (1990)
J Clin Microbiol
28:2064-2068).
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
E. faecalis
infection.
The present invention encompasses isolated nucleic acids and polypeptides derived from
E. faecalis
that are useful as reagents for diagnosis of bacterial disease, components of effective antibacterial vaccines, and/or as targets for antibacterial drugs, including anti-
E. faecalis
drugs. They can also be used to detect the presence of
E. faecalis
and other Enterococcus species in a sample; and in screening compounds for the ability to interfere with the
E. faecalis
life cycle or to inhibit
E. faecalis
infection. They also has use as biocontrol agents for plants.
The present invention also provides a genome-wide comparison by FASTA of the predicted amino acid sequences of several
E. faecalis
open reading frames (ORFs) with the predicted amino acid sequence of several
E. faecium
ORFs (Table 3). Together,
E. faecalis
and
E. faecium
account for >95% of all VRE infections. Genomic comparison of
E. faecalis
with
E. faecium
at the sequence, open reading frame (ORF), and gene level provides valuable information on shared targets, which can be exploited in designing diagnostics and therapeutics for VRE. Identifying common essential genes through sequencing and analysis of both genomes provides a much quicker route to these targets, and speeds the progress of probe design for identification of VRE infection, and vaccine compositions for protection from and treatment of these infections.
More specifically, this invention features compositions of nucleic acids corresponding to entire coding sequences of
E. faecalis
proteins, including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from
E. faecalis
proteins to block protein translation, and methods for producing
E. faecalis
proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention a
Bush David
Doucette-Stamm Lynn A.
Genome Therapeutics Corporation
Mosher Mary E.
LandOfFree
Nucleic acid and amino acid sequences relating to... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleic acid and amino acid sequences relating to..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid and amino acid sequences relating to... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3031046