A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans

被引:156
作者
Paton, AW
Morona, R
Paton, JC [1 ]
机构
[1] Womens & Childrens Hosp, Mol Microbiol Unit, Adelaide, SA 5006, Australia
[2] Univ Adelaide, Dept Microbiol & Immunol, Adelaide, SA 5005, Australia
基金
英国医学研究理事会;
关键词
D O I
10.1038/73111
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gastrointestinal disease caused by Shiga toxin-producing bacteria (such as Escherichia coli O157:H7 and Shigella dysenteriae) is often complicated by life-threatening toxin-induced systemic sequelae, including hemolytic-uremic syndrome. Such infections can now be diagnosed very early in the course of the disease, but at present no effective therapeutic intervention is possible. Here, we constructed a recombinant bacterium that displayed a Shiga toxin receptor mimic on its surface, and it adsorbed and neutralized Shiga toxins with very high efficiency. Moreover, oral administration of the recombinant bacterium completely protected mice from challenge with an otherwise 100%-fatal dose of Shiga toxigenic E. coli. Thus, the bacterium shows great promise as a 'probiotic' treatment for Shiga toxigenic E. coli infections and dysentery.
引用
收藏
页码:265 / 270
页数:6
相关论文
共 37 条
[1]   INVESTIGATION OF SHIGA-LIKE TOXIN BINDING TO CHEMICALLY SYNTHESIZED OLIGOSACCHARIDE SEQUENCES [J].
ARMSTRONG, GD ;
FODOR, E ;
VANMAELE, R .
JOURNAL OF INFECTIOUS DISEASES, 1991, 164 (06) :1160-1167
[2]   A PHASE-I STUDY OF CHEMICALLY SYNTHESIZED VEROTOXIN (SHIGA-LIKE TOXIN) PK-TRISACCHARIDE RECEPTORS ATTACHED TO CHROMOSORB FOR PREVENTING HEMOLYTIC-UREMIC SYNDROME [J].
ARMSTRONG, GD ;
ROWE, PC ;
GOODYER, P ;
ORRBINE, E ;
KLASSEN, TP ;
WELLS, G ;
MACKENZIE, A ;
LIOR, H ;
BLANCHARD, C ;
AUCLAIR, F ;
THOMPSON, B ;
RAFTER, DJ ;
MCLAINE, PN .
JOURNAL OF INFECTIOUS DISEASES, 1995, 171 (04) :1042-1045
[3]   ADJUVANT ACTIVITY OF ESCHERICHIA-COLI HEAT-LABILE ENTERO-TOXIN AND EFFECT ON THE INDUCTION OF ORAL TOLERANCE IN MICE TO UNRELATED PROTEIN ANTIGENS [J].
CLEMENTS, JD ;
HARTZOG, NM ;
LYON, FL .
VACCINE, 1988, 6 (03) :269-277
[4]   PROCEDURE FOR ISOLATION OF BACTERIAL LIPOPOLYSACCHARIDES FROM BOTH SMOOTH AND ROUGH PSEUDOMONAS-AERUGINOSA AND SALMONELLA-TYPHIMURIUM STRAINS [J].
DARVEAU, RP ;
HANCOCK, REW .
JOURNAL OF BACTERIOLOGY, 1983, 155 (02) :831-838
[5]  
DEGRANDIS S, 1989, J BIOL CHEM, V264, P12520
[6]   GENETIC-LOCUS FOR THE BIOSYNTHESIS OF THE VARIABLE PORTION OF NEISSERIA-GONORRHOEAE LIPOOLIGOSACCHARIDE [J].
GOTSCHLICH, EC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (06) :2181-2190
[7]   The assembly system for the outer core portion of R1- and R4-type lipopolysaccharides of Escherichia coli -: The R1 core-specific β-glucosyltransferase provides a novel attachment site for O-polysaccharides [J].
Heinrichs, DE ;
Yethon, JA ;
Amor, PA ;
Whitfield, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (45) :29497-29505
[8]   CLONING AND NUCLEOTIDE SEQUENCING OF VERO TOXIN 2 VARIANT GENES FROM ESCHERICHIA-COLI O91-H21 ISOLATED FROM A PATIENT WITH THE HEMOLYTIC UREMIC SYNDROME [J].
ITO, H ;
TERAI, A ;
KURAZONO, H ;
TAKEDA, Y ;
NISHIBUCHI, M .
MICROBIAL PATHOGENESIS, 1990, 8 (01) :47-60
[9]   Molecular analysis of a locus for the biosynthesis and phase-variable expression of the lacto-N-neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis [J].
Jennings, MP ;
Hood, DW ;
Peak, IRA ;
Virji, M ;
Moxon, ER .
MOLECULAR MICROBIOLOGY, 1995, 18 (04) :729-740
[10]   CONSTRUCTION OF VECTORS WITH THE P15A REPLICON, KANAMYCIN RESISTANCE, INDUCIBLE LACZ-ALPHA AND PUC18 OR PUC19 MULTIPLE CLONING SITES [J].
JOBLING, MG ;
HOLMES, RK .
NUCLEIC ACIDS RESEARCH, 1990, 18 (17) :5315-5316