Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
2001-08-10
2004-12-21
Martinell, James (Department: 1631)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S252300, C435S320100, C435S006120, C536S023100, C536S023400, C536S023700
Reexamination Certificate
active
06833253
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to novel
Staphylococcus aureus
genes (
S. aureus
) nucleic acids and polypeptides. Also provided are vectors, host cells and recombinant or synthetic methods for producing the same. Further provided are diagnostic methods for detecting
S. aureus
using probes, primers, and antibodies to the
S. aureus
nucleic acids and polypeptides of the present invention. The invention further relates to screening methods for identifying agonists and antagonists of
S. aureus
polypeptide activity and to vaccines using
S. aureus
nucleic acids and polypeptides and to therapeutics using agonists and/or antagonists of the invention.
BACKGROUND OF THE INVENTION
The genus
Staphylococcus
includes at least 20 distinct species. (For a review see Novick, R. P., The
Staphylococcus
as a Molecular Genetic System in MOLECULAR BIOLOGY OF THE STAPHYLOCOCCI, 1-37 (R. Novick, Ed., VCH Publishers, New York (1990)). Species differ from one another by 80% or more, by hybridization kinetics, whereas strains within a species are at least 90% identical by the same measure.
The species
S. aureus
, a gram-positive, facultatively aerobic, clump-forming cocci, is among the most important etiological agents of bacterial infection in humans, as discussed briefly below.
Human Health and
S. aureus
Staphylococcus aureus
is a ubiquitous pathogen. See, e.g., Mims et al., MEDICAL MICROBIOLOGY (Mosby-Year Book Europe Limited, London, UK 1993). It is an etiological agent of a variety of conditions, ranging in severity from mild to fatal. A few of the more common conditions caused by
S. aureus
infection are bums, cellulitis, eyelid infections, food poisoning, joint infections, neonatal conjunctivitis, osteomyelitis, skin infections, surgical wound infection, scalded skin syndrome and toxic shock syndrome, some of which are described further below.
Burns: Burn wounds generally are sterile initially. However, they generally compromise physical and immune barriers to infection, cause loss of fluid and electrolytes and result in local or general physiological dysfunction. After cooling, contact with viable bacteria results in mixed colonization at the injury site. Infection may be restricted to the non-viable debris on the burn surface (“eschar”), it may progress into full skin infection and invade viable tissue below the eschar and it may reach below the skin, enter the lymphatic and blood circulation and develop into septicemia.
S. aureus
is among the most important pathogens typically found in burn wound infections. It can destroy granulation tissue and produce severe septicemia.
Cellulitis: Cellulitis, an acute infection of the skin that expands from a typically superficial origin to spread below the cutaneous layer, most commonly is caused by
S. aureus
in conjunction with
S. pyrogenes
. Cellulitis can lead to systemic infection. In fact, cellulitis can be one aspect of synergistic bacterial gangrene. This condition typically is caused by a mixture of
S. aureus
and microaerophilic
Streptococci
. It causes necrosis and treatment is limited to excision of the necrotic tissue. The condition often is fatal.
Eyelid infections:
S. aureus
is the cause of styes and of “sticky eye” in neonates, among other eye infections. Typically such infections are limited to the surface of the eye, and may occasionally penetrate the surface with more severe consequences.
Food poisoning: Some strains of
S. aureus
produce one or more of five serologically distinct, heat and acid stable enterotoxins that are not destroyed by digestive process of the stomach and small intestine (enterotoxins A-E). Ingestion of the toxin, in sufficient quantities, typically results in severe vomiting, but not diarrhea. The effect does not require viable bacteria. Although the toxins are known, their mechanism of action is not understood.
Joint infections:
S. aureus
infects bone joints causing diseases such osteomyelitis. See, e.g., R. Cunningham et al., (1996) J. Med. Microbiol. 44:157-164.
Osteomyelitis:
S. aureus
is the most common causative agent of haematogenous osteomyelitis. The disease tends to occur in children and adolescents more than adults and it is associated with non-penetrating injuries to bones. Infection typically occurs in the long end of growing bone, hence its occurrence in physically immature populations. Most often, infection is localized in the vicinity of sprouting capillary loops adjacent to epiphysis growth plates in the end of long, growing bones.
Skin infections:
S. aureus
is the most common pathogen of such minor skin infections as abscesses and boils. Such infections often are resolved by normal host response mechanisms, but they also can develop into severe internal infections. Recurrent infections of the nasal passages plague nasal carriers of
S. aureus.
Surgical Wound Infections: Surgical wounds often penetrate far into the body. Infection of such wound thus poses a grave risk to the patient.
S. aureus
is the most important causative agent of infections in surgical wounds.
S. aureus
is unusually adept at invading surgical wounds; sutured wounds can be infected by far fewer
S. aureus
cells then are necessary to cause infection in normal skin. Invasion of surgical wound can lead to severe
S. aureus
septicemia. Invasion of the blood stream by
S. aureus
can lead to seeding and infection of internal organs, particularly heart valves and bone, causing systemic diseases, such as endocarditis and osteomyelitis.
Scalded Skin Syndrome:
S. aureus
is responsible for “scalded skin syndrome” (also called toxic epidermal necrosis, Ritter's disease and Lyell's disease). This diseases occurs in older children, typically in outbreaks caused by flowering of
S. aureus
strains produce exfoliation(also called scalded skin syndrome toxin). Although the bacteria initially may infect only a minor lesion, the toxin destroys intercellular connections, spreads epidermal layers and allows the infection to penetrate the outer layer of the skin, producing the desquamation that typifies the diseases. Shedding of the outer layer of skin generally reveals normal skin below, but fluid lost in the process can produce severe injury in young children if it is not treated properly.
Toxic Shock Syndrome: Toxic shock syndrome is caused by strains of
S. aureus
that produce the so-called toxic shock syndrome toxin. The disease can be caused by
S. aureus
infection at any site, but it is too often erroneously viewed exclusively as a disease solely of women who use tampons. The disease involves toxemia and septicemia, and can be fatal.
Nosocomial Infections: In the 1984 National Nosocomial Infection Surveillance Study (“NNIS”)
S. aureus
was the most prevalent agent of surgical wound infections in many hospital services, including medicine, surgery, obstetrics, pediatrics and newborns.
Other Infections: Other types of infections, risk factors, etc. involving
S. aureus
are discussed in: A. Trilla (1995) J. Chemotherapy 3:37-43; F. Espersen (1995) J. Chemotherapy 3:11-17; D. E. Craven (1995) J. Chemotherapy 3:19-28; J. D. Breen et al. (1995) Infect. Dis. Clin. North Am. 9(1):11-24 (each incorporated herein in their entireties).
Resistance to Drugs of
S. aureus
Strains
Prior to the introduction of penicillin the prognosis for patients seriously infected with
S. aureus
was unfavorable. Following the introduction of penicillin in the early 1940s even the worst
S. aureus
infections generally could be treated successfully. The emergence of penicillin-resistant strains of
S. aureus
did not take long, however. Most strains of
S. aureus
encountered in hospital infections today do not respond to penicillin; although, fortunately, this is not the case for
S. aureus
encountered in community infections. It is well-known now that penicillin-resistant strains of
S. aureus
produce a lactamase which converts penicillin to pencillinoic acid, and thereby destroys antibiotic activity. Furthermore, the lactamase gene often is propagated episomally, typically on a plasmid, a
Human Genome Sciences Inc.
Human Genome Sciences Inc.
Martinell James
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