Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-06-04
2003-05-13
Borin, Michael (Department: 1631)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100
Reexamination Certificate
active
06562958
ABSTRACT:
BACKGROUND OF THE INVENTION
The genus Acinetobacter is divided into at least 21 species by 16S ribosomal sequence analysis (Ibrahim, A., et al, 1997, Int J Syst Bacteriol. 47:837-841). They are gram-negative, oxidase-negative, non-motile, nitrate-negative, nonfermentative rods. The closest related lineage to Acinetobacter is the Moraxella genus. The glucose-oxidizing, nonhemolytic
Acinetobacter baumannii
(
A. baumannii
, spelling variants
A. baumanii
and
A. baumanni
), formerly known as
Acinetobacter calcoaceticus
var.
anitratus
, is the most frequently isolated species in this genus. This organism is commonly found in the environment as well as in hospitals. (Alexander Von Graevenitz, Acinetobacter, Alcaligenes, Moraxella, and Other Nonfermentative Gram-Negative Bacteria Chap. 41, Manual of Clinical Microbiology, Sixth Edition, Editor, Patrick R. Murry, ASM Press, Washington D.C., 1995)
A. baumannii
has only recently been recognized as a nosocomial pathogen. Invasive techniques such as surgery, and pulmonary ventilation combined with immunocompromized patients, have lead to the development and increased importance of the Acinetobacter genus as nosocomial pathogens (Towner, K., et al, 1997, Med Microbiol. 46: 721-746).
A. baumannii
has been associated with bacteremia, septicemia, pneumonia, meningitis, and infections of burns, urinary tract and surgical wounds. Often these diseases are nosocomial in origin. The ability of
A. baumannii
to survive on dry surfaces for long periods of time has contributed to outbreaks in hospitals. These outbreaks have been traced to reusable pressure transducers, room humidifiers, mattresses, pillows, and components of ventilation equipment (Constanze, W., et al, 1997, J Clin Microbiol. 35: 1394-1397). Outbreaks have also been associated with respiratory therapy equipment, intravascular access devices, and the hands of care-givers (Marques, M., et al, 1997, J Hosp Infect. 37:125-135). The mortality rate of nosocomial infections by
A. baumannii
can be quite high. The mortality rate of meningitis caused by
A. baumannii
is 20% to 27%, and bacteremia mortality ranges from 19% to 44% (Jimenez-Mejias, M., et al, 1997, Clin Infect Dis. 24: 932-935).
Resistance to antibiotics by the genus Acinetobacter has increased over time, with
A. baumannii
usually being the most resistant.
A. baumannii
is becoming resistant to many compounds that it was previously susceptible to, such as floroquinolones, aminoglycosides, ceftazidime, ticarcillin, and imipenem (Duval, J., et al, 1994, J Clin Microbiol 32: 2677-2681). In one study, at least 82% of the
A. baumannii
isolates were resistant to piperacillin, gentamicin, amikacin, netrilaicin, ceftazidime, cefotaxime, and norfloxacin (Garcia, D., et al, 1996, J Hosp Infect. 34:139-144). Resistance to ciprofloxacin in
A. baumannii
isolated from ICU patients, has increased from 4% in 1986 to 34% in 1993. Acinetobacter clinical isolates may be resistant to any of the therapeutically relevant antibiotics, and resistance is influenced by selection pressure of the preferred antibiotic (Towner, K., et al, 1997, Med Microbiol. 46: 721-746).
The Acinetobacter genus, with
A. baumannii
playing the lead role, is becoming increasingly important pathogens. Thirty years ago, the Acinetobacter genus was considered environmental and non-pathogenic. Currently, they are responsible for 1-2% of all nosocomial infections. They infect the very ill and most clinical isolates are multidrug resistant. Furthermore, they are capable of increasing hospitalization and causing epidemics (Towner, K., et al, 1997, Med Microbiol. 46: 721-746).
SUMMARY OF THE INVENTION
The present invention fulfills the need for diagnostic tools and therapeutics by providing bacterial-specific compositions and methods for detecting Acinetobacter species including
A. baumannii
, as well as compositions and methods useful for treating and preventing Acinetobacter infection, in particular,
A. baumannii
infection, in vertebrates including mammals.
The present invention encompasses isolated nucleic acids and polypeptides derived from
A. baumannii
that are useful as reagents for diagnosis of bacterial disease, components of effective antibacterial vaccines, and/or as targets for antibacterial drugs including anti-
A. baumannii
drugs. They can also be used to detect the presence of
A. baumannii
and other Acinetobacter species in a sample; and in screening compounds for the ability to interfere with the
A. baumannii
life cycle or to inhibit
A. baumannii
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
A. baumannii
proteins, including surface or secreted proteins or parts thereof, nucleic acids capable of binding mRNA from
A. baumannii
proteins to block protein translation, and methods for producing
A. baumannii
proteins or parts thereof using peptide synthesis and recombinant DNA techniques. This invention also features antibodies and nucleic acids useful as probes to detect
A. baumannii
infection. In addition, vaccine compositions and methods for the protection or treatment of infection by
A. baumannii
are within the scope of this invention.
The nucleotide sequences provided in SEQ ID NO:1-SEQ ID NO:4126, 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:4126 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:4126, 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:4126. 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 WordPerfect and Microsoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A person skilled in the art can readily adapt any number of data processor structuring formats (e.g. text file or database) in order to obtain computer rea
Breton Gary
Bush David
Borin Michael
Genome Therapeutics Corporation
Genome Therapeutics Corporation
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