Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1999-03-31
2001-02-13
Housel, James (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S184100, C424S185100, C424S192100, C530S350000, C530S825000, C435S007100, C435S810000
Reexamination Certificate
active
06187321
ABSTRACT:
BACKGROUND OF THE INVENTION
Pathogenic
Escherichia coli
(“
E. coli
”) is the causative agent of a variety of diseases in humans and animals, and often have the ability to avoid, resist or inactivate a multi-cellular organisms chemical and cellular defenses for a significant period of time after the host has been exposed to the pathogen.
E. coli
infection of the avian respiratory tract causes respiratory tract lesions and septicemia.
E. coli
infections are often secondary to infections of birds by infectious bronchitis virus, Newcastle disease virus and Mycoplasma spp (Gross,
Disease of Poultry
, 8th ed., 270-278 (1984)). Three components present on the cell surface of
E. coli
assist in promoting the survival of
E. coli
from serum and phagocytosis (Timmis et al.,
Current Topics in Micro. and Immunol
., 118:197-218 (1985)). These three components are the acidic polysaccharide capsules, O-antigen lipopolysaccharide (“O-antigens”) and outer membrane proteins (“OMPs”). Some types of O-antigens have been shown to mediate resistance to complement and to increase bacterial virulence (Moll et al.,
FEMS Lett
., 6:273-276 (1979); Pluschke et al., Infect. Immun., 42:907-913 (1983); and Goldman et al.,
J. Bacteriol
., 159:877-882 (1984)). Avian
E. coli
strains with one of three O-antigens, O1, O2 or O3, cause the majority of all
E. coli
-induced septicemic colibacillosis in birds (Naveh et al.,
Avian Disease
, 28:651-661 (1984)). However, many other serotypes such as O78:K80 are also observed.
Septicemic colibacillosis occurs most commonly in 5 to 12-week old broiler chickens, but also occurs in newly hatched chicks and turkey poults. The pathogenicity of
E. coli
for poultry has been correlated with various factors (Sussman,
The Virulence of Escherichia coli
, Academic Press Inc., Ltd., London (1985)). These factors include antimicrobial resistance (Cloud et al.,
Avian Dis
., 29:1084-1093 (1985)); production of colicins, siderophores, type I pili and hemolysins (Arp et al.,
Avian Dis
., 24:153-161 (1980)); resistance to host complement (Ike et al.,
J. Vet. Med. Sci
., 54:1091-1098 (1992)); presence of certain plasmids (Binns et al.,
Nature
, 279:778-781 (1979)); motility (Wooley et al.,
Avian Dis
., 36:679-684 (1992)); serotype, e.g., O1, O2, O3 and O78 (Rosenberger et al.,
Avian Dis
., 22:1094-1107 (1985)); and invasiveness (Vidotto et al.,
Avian Dis
., 34:531-538 (1990)). Recent reports have shown that the ability of avian
E. coli
to resist the lytic effects of host complement is a major factor in the development of colibacillosis in poultry (Nolan et al.,
Avian Dis
., 38:146-150 (1994); Nolan et al.,
Avian Dis
., 36:395-397 (1992); Nolan et al.,
Avian Dis
., 3:398402 (1992)).
Two well-defined, interacting components that constitute the major first-line of host defenses against invading bacteria are the complement system and phagocytosis (Mims, C. A.,
The Pathogenesis of Infectious Disease
, 2nd edn. Academic, London (1982); Taylor, P. W.,
Microbiol. Rev
., 47:46-83 (1983)). Phagocytosis involves the ingestion of particulate material, including whole pathogenic microorganisms. In phagocytosis, the plasma membrane expands around the particulate material to form phagosomes. Only specialized cells, phagocytes, are involved in phagocytosis and include such cells as blood monocytes, neutrophils and tissue macrophages.
Complement resistance of
E. coli
has generally been reported as related to several potential structural factors including a K1-antigenic capsule (Aqüero et al.,
Infect. Immun
., 40:359-368 (1984)), or other capsule type (Russo et al.,
Infect. Immun
., 61:3578-3582 (1993)), a smooth lipopolysaccharide (LPS) layer (Cross et al., In:
Bacteria, Complement and the Phagocytic Cell
, Vol. H24, F. C. Cabello and C. Pruzzo, eds., Springer-Verlag, Berlin, pp. 319-334 (1988)), and certain OMPs including TraT (Montenegro et al.,
J. Gen. Microbiol
. 131:1511-1521 (1985); Moll et al.,
Infect. Immun
. 2:359-367 (1980)), Iss (Binns et al.,
Infect. Immun
., 35:654-659 (1982); Chuba et al.,
Mol. Gen. Genet
., 216:287-192 (1989)), and OmpA (Weiser et al.,
Infect. Immun
. 59:2252-2258 (1991)). The absence of capsule as a complement-resistance mechanism in disease-associated avian
E. coli
isolates suggests that such isolates must employ other means to avoid the killing effects of complement.
Iss is an OMP encoded by an avian
E. coli iss
gene. Some reports have indicated that
E. coli
isolates from avian subjects with a septicemic disease are much more likely to have iss-related sequences than are
E. coli
isolates of apparently healthy birds. However, no significant difference in the distribution of traT-related sequences (traT encodes the OMP TraT) has been found in the same isolates. The plasmid location of iss and traT suggests that their presence in different isolates might be more variable than the chromosomally-located ompA gene (Weiser et al.,
Infect. Immun
., 59:2252-2258 (1991)).
The expression of a human
E. coli iss
gene was found to increase the virulence of
E. coli
containing the gene by 100-fold for one-day old chicks and to increase the complement resistance of transformed cells over 20-fold for one-day old chicks (Binns et al.,
Infect. Immun
., 35:654-659 (1982)). Genetic evidence suggests that iss obtained from human
E. coli
is a derivative of a lambda gene known as bor (Barondess et al.,
J. Bacteriol
., 177:1247-1253 (1995); Barondess et al.,
Nature
, 346:871-874; (1990); Chuba et al.,
Mol. Gen. Genet
., 216:287-292 (1989)). Bor is a lipoprotein of the cell envelope of
E. coli
lambda lysogens and appears to confer serum resistance on these lysogens. (Barondess et al.,
J. Bacteriol
., 177:1247-1253 (1995)). The high sequence identity between the Bor polypeptide and an avian Iss polypeptide suggests that Iss is also targeted to the outer membrane.
Septicemic colibacillosis is an economically devastating problem for the poultry industry in the United States. It is the most costly bacterial disease of production poultry animals causing multi-million dollar losses by the poultry industry annually. Control of this disease is hampered by the lack of a basic understanding about the virulence mechanisms employed by avian
E. coli
. For example, no single identifiable virulence marker has been associated with disease-causing avian
E. coli
. In other animal species, such as cattle, certain markers of virulence have been identified, and these markers have been used to facilitate epidemiologic studies and to develop control strategies designed to decrease the detrimental impact of colibacillosis on animal agriculture (Butler et al.,
G.L. Gyles ed. CAB International
, Wallingford, UK:91-116 (1994)).
Therefore, a need exists to identify genes and other markers associated with complement-resistance of
E. coli
in birds. These genes can function as markers for disease-causing avian
E. coli
and the detection of these genes may form the basis for improved diagnostic and control strategies for avian colibacillosis, in addition to the formulation and preparation of immunogenic compositions useful to prevent or inhibit avian septicemic diseases.
SUMMARY OF THE INVENTION
iss has been identified as a marker for avian
E. coli
virulence and complement-resistance, and is associated with septicemic disease in birds. As used herein, the term iss or iss “gene” refers to a nucleic acid sequence or molecule that encodes an avian
E. coli
Iss polypeptide. Thus, the present invention provides an isolated and purified nucleic acid molecule that encodes an avian
E. coli
Iss polypeptide, a biologically active variant or subunit thereof. However, as described more fully below, an “Iss polypeptide” also includes an Iss “fusion” polypeptide.
A biologically active Iss polypeptide, variant or subunit thereof falling within the scope of the invention has at least about 1%, preferably at least about 10%, more preferably at least about 50%, and even more preferably at least about 90%, the activity of the polypeptide comprising SEQ ID NO:2. A preferred n
Horne Shelley M.
Nolan Lisa K.
Robinson Michael
Devi S.
Housel James
Mueting Raasch & Gebhardt, P.A.
North Dakota State University
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