title: Enterobacterial tumor colonization in mice depends on bacterial metabolism and macrophages but is independent of chemotaxis and motility.
abstract: Despite promising results and increasing attention in bacterial cancer therapy, surprisingly little is known about initial tumor colonization and the interaction between bacteria and surrounding tumor tissue. Here, we analyzed the role of chemotaxis, motility, and metabolism both in Escherichia coli and Salmonella enterica serovar Typhimurium strains upon intravenous injection into tumor-bearing mice. In contrast to previous models, we found that chemotaxis and motility do not play a significant role in tumor colonization and bacterial distribution within the tumor. Rather, the whole colonization and intratumoral migration process seems to be a passive mechanism that is influenced by the reticuloendothelial system of the host, by the tumor microenvironment and by the bacterial metabolism. These conclusions were supported by experimental data demonstrating that disruption of the basic branch of the aromatic amino acid biosynthetic pathway and depletion of macrophages, in contrast to flagellar mutations, led to significant changes in bacterial accumulation in tumors of live mice.
authors.affiliation: Genelux Corporation, 3030 Bunker Hill Street, San Diego, CA 92109-5754, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Stritzker
authors.forename: Stephanie
authors.initials: S
authors.lastname: Weibel
authors.forename: Carolin
authors.initials: C
authors.lastname: Seubert
authors.forename: Andreas
authors.initials: A
authors.lastname: Götz
authors.forename: Achim
authors.initials: A
authors.lastname: Tresch
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Oelschlaeger
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: D024322:Amino Acids, Aromatic / Q000378:metabolism; D000818:Animals; D058491:Bacterial Load; D053898:Biosynthetic Pathways / Q000235:genetics; D002633:Chemotaxis; D004926:Escherichia coli / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008124:Locomotion; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009369:Neoplasms / Q000276:immunology / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D024322:Amino Acids, Aromatic