Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Reexamination Certificate
1999-07-09
2002-08-13
Peselev, Elli (Department: 1623)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
C435S072000
Reexamination Certificate
active
06432681
ABSTRACT:
FIELD OF THE INVENTION
The instant invention relates to a method for determining susceptibility to
Escherichia coli
urinary tract infections (UTI) and corresponding methods for diagnosing secretors and nonsecretors of histo-blood group antigens based on assaying urogenital cells and secretions. The instant invention also relates to methods and compositions for preventing and treating
E. coli
urinary tract infections. For example, disialosyl galactosyl-globoside is useful for diagnostic purposes and sialosyl galactosyl-globoside is useful for treatment and prevention of UTI.
BACKGROUND OF THE INVENTION
Among the most common bacterial infections encountered in clinical practice are urogenital mucosal infections caused by
E. coli, Chiamydlia trachomatis
and
N. gonorrheae
which are diagnosed and treated at a cost to society in the billions of dollars. These infections are frequently recurrent and efforts at prevention have been largely fruitless, in part because of the apparent ineffectiveness of the mucosal immune system. Mucosal immunity is short-lived and in the long term, not protective. Despite much effort, attempts to develop vaccines against these mucosal urogenital pathogens have not succeeded and even natural immunity does not protect against recurrent episodes of infection with these agents. In addition, antigenic variability of the organisms has complicated vaccine development.
In particular, acute uncomplicated urinary tract infections occur in millions of young women each year. While most of these women experience only single or sporadic infections, approximately 20% suffer very frequent (≧3/year) recurrences (Mabeck, C. E.,
Postgrad. Med J
., 48:69-75, 1972). The apparent increased susceptibility to urinary tract infection in these patients cannot be explained by underlying functional or anatomic abnormalities of the urinary tract, but instead appears to arise from the interaction of infecting
E. coli
strains with these patients' epithelial cells.
Thus, women prone to frequent recurrences demonstrate prolonged colonization of the vaginal mucosa with
E. coli
, the predominant causative species in these infections, (Stamey, T. A. et al.,
J. Urol
, 113:214-217, 1975) and three-fold more
E. coli
adhere to vaginal, buccal and uroepithelial cells from women with recurrent urinary tract infection than to cells from control patients (Schaeffer, A. J. et al.,
N. Engl. J. Med
., 304:1062-1066, 1981; Svanborg-Eden, C. et al.,
Infect. Immun
., 26:837-840, 1979). Women with a history of recurrent urinary tract infections are also more likely to be nonsecretors of histo-blood group antigens than are women without a history of infections (relative risk=3 to 4 (Kinane, D. F. et al.,
Br. Med. J
., 285:7-9, 1982; Sheinfeld, J. et al.,
N. Engl. J. Med
., 320:773-777, 1989; Hooton, T. M. et al.,
Twenty
-
ninth Interscience Conference on Antimicrobial Agents and Chemotherapy
, 8, 1989 (Program and Abstracts); Lomberg, H. et al.,
Infect. Immun
., 51:919-926, 1986)), and
E. coli
adhere in greater numbers to uroepithelial cells from nonsecretors (Lomberg, H. et al.,
Infect. Immun
., 51:919-926, 1986).
E. coli
adhesins also play an important role in the pathogenesis of urinary tract infection (Stapleton, A. et al.,
J. Infect Dis
., 163:773-779, 1989; Johnson, J. R.,
J. Infect. Dis
., 156:225-229, 1987; Jacobson, S. H. et al.,
J. Infect. Dis
., 152:426-427, 1985; Vaisenen, V. et al.,
Lancet
, 2:1366-1369, 1981; Kallenius, G. et al.,
Lancet
, 2:1369-1372, 1981; Vaisanen-Rhen, V. et al.,
Infect. Immun
., 48:149-155, 1984; Westerlund, B. et al.,
J. Infect. Dis
., 158:996-1002, 1988; Arthur, M. et al.,
Infect. Immun
., 57:303-313, 1989; Sandberg, T., B. Kaijser,
J. Clin. Microbiol
, 26:1471-1476, 1988; O'Hanley, P. et al.,
N. Engl. J. Med
., 313:414-420, 1985; Lidefelt, K.-J. et al.,
Acta Paediatr. Scand
., 76:775-780, 1987; Lund, B. et al.,
Mol. Microbiol
., 2:255-263, 1988), particularly the genetically related P and F adhesins.
P adhesins are present in 50% to 65% of
E. coli
strains causing cystitis (Stapleton, A. et al.,
J. Infect Dis
., 163:773-779, 1989; Arthur, M. et al.,
Infect. Immun
., 57:303-313, 1989; Sandberg, T., B. Kaijser,
J. Clin. Microbiolp
, 26:1471-1476, 1988; O'Hanley, P. et al.,
N. Engl. J. Med
., 313:414-420, 1985; Lidefelt, K.-J. et al.,
Acta Paediatr. Scand
., 76:775-780, 1987; Lund, B. et al.,
Mol. Microbiol
., 2:255-263, 1988) and 75% to 90% of isolates from pyelonephritis (Johnson, J. R.,
J. Infect. Dis
., 156:225-229, 1987; Jacobson, S. H. et al.,
J. Infect. Dis
., 152:426-427, 1985; Vaisenen, V. et al.,
Lancet
, 2:1366-1369, 1981; Kallenius, G. et al.,
Lancet
, 2:1369-1372, 1981; Vaisanen-Rhen, V. et al.,
Infect. Immun
., 48:149-155, 1984; Westerlund, B. et al.,
J. Infect. Dis
., 158:996-1002, 1988; Arthur, M. et al.,
Infect. Immun
., 57:303-313, 1989; Sandberg, T., B. Kaijser,
J. Clin. Microbiol
, 26:1471-1476, 1988). The minimal receptor for the P adhesin is the galactose &agr;1-4 galactose moiety, present in the globoseries glycolipids and the P
1
blood group antigen (Kallenius, G. et al.,
FEMS Microbiol Lett
., 7:297-302, 1980; Leffler, H. et al.,
FEMS Microbiol. Lett
., 8:127-134, 1980; Svanborg-Eden, C. et al.,
Scand. J Infect Dis. Suppl
., 24:144-147, 1980; Kallenius, G. et al.,
Infection
, 8 (Suppl. 3):S288-S293, 1981; Kallenius, G. et al.,
Lancet
, 2:604-606, 1981; Leffler, H. et al.,
Infect Immun
., 34:920-929, 1981; Kallenius, G. et al.,
Scand. J. Infect. Dis. Suppl
., 33:52-60, 1982; Svenson, S. B. et al.,
Infection
, 11:73/61-79/67, 1983; Bock, K. et al.,
J. Biol Chem
., 260:8545-8551, 1985).
F adhesins are expressed in 30% to 65% of urinary tract infection isolates (Stapleton, A. et al.,
J. Infect Dis
., 163:773-779, 1989; Arthur, M. et al.,
Infect. Immun
., 57:303-313, 1989). The minimal binding moiety for the F adhesin is less well defined and probably more complex; proposed receptors include the Forssman and para-Forssman antigens, globoside, galactosyl globoside, globo A and globo H, and stage-specific embryonic antigen-4 (SSEA-4) (Lund, B. et al.,
Mol. Microbiol
., 2:255-263, 1988; Lindstedt, R. et al.,
Infect. Immun
., 57:3389-3394, 1989; Karr, J. F. et al.,
Infect Immun
., 58:4055-4062, 1990; Stromberg, N. et al.,
EMBO J
., 9:2001-2010, 1990). The globoseries glycolipids have recently been shown to be modified by the histo-blood group status, and ABH active globoseries GSLs are found in renal epithelium and in voided uroepithelial cells as well as on erythrocytes (Leffler, H. et al.,
FEMS Microbiol. Lett
., 8:127-134, 1980; Bock, K. et al.,
J. Biol Chem
., 260:8545-8551, 1985; Breimer, M. E. et al.,
FEBS Lett
, 179:165-172, 1985; Breimer, M. E. et al.,
J. Biochem
., 98:1169-1180, 1985; Lindstedt, R. et al.,
Infect. Immun
., 59:1086-1092, 1991; Clausen, H. et al.,
Vox Sang
., 56:1-20, 1989; Kannagi, R. et al.,
FEBS Lett
., 175:397-401, 1984; Clausen, H. et al.,
Biochem. Biophys. Res. Commun
., 124:523-529, 1984).
Several lines of evidence have suggested that the increased susceptibility to recurrent urinary tract infection observed in some otherwise healthy women may be explained by genetic factors influencing the density and/or specificity of bacterial receptors available to mediate colonization of their uroepithelial cells (Schaeffer, A. J. et al.,
N. Engl. J. Med
., 304:1062-1066, 1981; Svanborg-Eden, C. et al.,
Infect. Immun
., 26:837-840, 1979; Kinane, D. F. et al.,
Br. Med. J
., 285:7-9, 1982; Sheinfeld, J. et al.,
N. Engl. J. Med
., 320:773-777, 1989; Hooton, T. M. et al.,
Twenty
-
ninth Interscience Conference on Antimicrobial Agents and Chemotherapy
, 8, 1989 (Program and Abstracts); Lomberg, H. et al.,
Infect. Immun
., 51:919-926, 1986). Although it is known that nonsecretors of histo-blood group antigens are overrepresented among women with a history of recurrent urinary tract infections (Kinane, D. F. et al.,
Br. Med. J
., 285:7-9, 1982; Sheinfeld, J. et al.,
N. Engl. J. Med
., 320:773-777, 1989; Hooton, T. M. et al.,
Twenty
Hakomori Sen-Itiroh
Nudelman Edward
Stamm Walter E.
Stapleton Ann
Peselev Elli
Roylance Abrams Berdo & Goodman L.L.P.
The Regents of the University of Washington
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