title: Myristoylation negative msbB-mutants of probiotic E. coli Nissle 1917 retain tumor specific colonization properties but show less side effects in immunocompetent mice.
abstract: Specific colonization of solid tumors by bacteria opens the way to novel approaches in both tumor diagnosis and therapy. However, even non-pathogenic bacteria induce responses by the immune system, which could be devastating for a tumor bearing patient. As such effects are caused e.g., by the lipid A moiety of the lipopolysaccharide, a msbB-mutant of the probiotic E. coli Nissle 1917 strain was investigated. Bacteria of the mutant strain did not show any growth defects in culture media when compared to wild-type E. coli Nissle 1917 but were unable to myristoylate lipid A, had less toxic effects on immunocompetent BALB/c mice, and were still able to specifically colonize tumors. Therefore, the modification of lipid A could result in bacterial strains that might be better suited for diagnosis and therapy of tumors than the corresponding wild-type strains, even if those are not considered pathogenic or are of probiotic background.
authors.affiliation: Genelux Corporation, San Diego, CA, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Stritzker
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hill
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Gentschev
authors.forename: Aladar A
authors.initials: AA
authors.lastname: Szalay
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001691:Biological Therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D008050:Lipid A / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009369:Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000628:therapy*; D019936:Probiotics / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D008050:Lipid A; D000217:Acyltransferases; C097895:MsbB protein, E coli