title: A non-specific effect of orally administered Escherichia coli.
abstract: A number of genetically modified bacteria able to deliver a therapeutic gene into target cells has already been tested. Apart from the expected effects of bacterial therapy, the therapeutic bacterial strain also mediates a non-specific effect independent of the gene to be delivered. In this regard, we have recently shown that oral administration of the bacterial strain Escherichia coli XL1-Blue via gastric gavage to rats leads to a non-specific decrease in expression of vascular endothelial growth factor (VEGF) in intestinal wall without corresponding changes in other parameters. We tried to adopt a model of intestinal ischemia and to treat the subsequent hypoxic condition using a strain carrying the effector plasmid encoding hypoxia-inducible factor 1 alpha (HIF-1alpha), as well as the helper plasmid encoding invasion and listeriolysin O. However, the model was ineffective, as obvious from macroscopic and molecular observations. We hypothesize that a competitive behavior of the administered strain in the intestinal microbiota leads to a decrease in activity of HIF-1alpha and reduction in expression of VEGF. Also, a functional disease model would be necessary for the invasion-expressing therapeutic strain to be effective. A different approach using bacterial protein delivery would possibly circumvent these bactofection-related problems.
authors.affiliation: Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia. romangardlik@gmail.com
authors.forename: Roman
authors.initials: R
authors.lastname: Gardlik
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007410:Intestinal Diseases / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000382:microbiology; D007511:Ischemia / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A