Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Bacteria or actinomycetales
Patent
1997-09-23
2000-12-12
Marx, Irene
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Bacteria or actinomycetales
4352529, A01N 6300, C12N 120
Patent
active
061594652
DESCRIPTION:
BRIEF SUMMARY
The present invention refers to Lactobacillus strains which have the ability to adhere to epithelial cell surfaces, especially in the human intestinal mucosa, and which can be used for the prophylactic and/or curative treatment of bacterial disturbances caused by pathogenic bacteria adhering to the epithelial cell in a similar way.
BACKGROUND OF THE INVENTION
The indigenous microbiota is one of the major defense mechanisms that protect the human or animal body against colonization by invading bacteria. Immunosuppressed, antibiotic treated and parenterally fed patients are at a risk of infectious diseases like sepsis, meningitis or urinary tract infections produced by spread of bacteria mainly deriving form the normal fecal population. One mechanism behind this process can be bacterial translocation, which is defined as the passage of viable bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs.
Blood poisoning, sepsis, is still a very common surgical complication in connection with abdominal surgery with a high death-rate. Bacteria or bacterial products may penetrate the malfunctioning intestinal wall and infect or induce malfunction in other remote organs, such as lungs, liver, heart etc. and this leads to multiple organ dysfunction or the so called intensive-care-disease. These patients are today treated by administration of antibiotics and surgical treatment of the abscess to the extent it could be located. At present antibiotics are conventionally administered before intestinal surgery in order to reduce the risk of postoperative infections and illness caused thereby. However, the treatment with antibiotics is associated with destruction of the normal intestinal flora and overgrowth with still more pathogenic bacteria.
These findings have led to an increased interest for microbial species which can beneficially affect the microbial balance of the host, e.g. by producing antimicrobial components or by competitive growing. Lactobacillus have been among the most studied species, and have in certain instances been shown to counteract the proliferation of pathogens.
Bacteria residing in the intestine may cause diseases in the colonized host such as diarrhoea in the intestines, or by secondarily colonizing normally sterile sites, such as the urinary tract, giving a urinary tract infection, or the blood stream, giving sepsis.
Pathogenic bacteria differ from those who do not provoke disease by the possession of so called virulence factors. An important virulence factor is the capacity to adhere to host cell carbohydrate receptor molecules. This is an important step, both because it enables colonization, and because it enables the delivery of toxins and other inflammatogenic substances in close proximity to the host cells. If delivered by an adherent bacterium, these toxic substances reach much higher concentrations locally than they would if they were secreted e.g. by bacteria residing in the intestinal lumen.
Bacteria causing urinary tract infection include Escherichia coli, Enterobacter, Klebsiella and Proteus, which all belong to the family Enterobacteriaceae. A majority of these bacteria possess type 1 fimbriae which confer the ability to adhere to mannose-containing receptors, for example on human vaginal epithelia cells and to the urinary slime protein Tamm-Horsefall protein. Type 1 fimbriae have been shown to be a virulence factor for cystitis, which can depend both on an increased ability to ascend into the urinary tract conferred by binding to vaginal and periurethral epithelial cells, as well as on an increased irritative effect caused by binding to epithelial cells in the urinary tract. [Thus only bacteria with type 1 fimbriae were able to induce a cytokine response, that is inflammation, in cultured urinary epithelial cells.]
Bacteria causing diarrhoea include Salmonella and Shigella, but intestinal overgrowth of Klebsiella or Enterobacter have also been associated with diarrhoea in young infants. It has been shown in the mouse that type 1 fimbriae are a virulen
REFERENCES:
patent: 5474932 (1995-12-01), Bengmark
patent: 5587314 (1996-12-01), Bengmark
Adlerberth Ingegerd
Ahrne Siv
Jeppsson Bengt
Johansson Marie-Louise
Molin Goran
Marx Irene
Probi AB
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