Enterobacterial tumor colonization in mice depends on bacterial metabolism and macrophages but is independent of chemotaxis and motility.
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.
Stritzker
Jochen
J
Genelux Corporation, 3030 Bunker Hill Street, San Diego, CA 92109-5754, USA.
Weibel
Stephanie
S
Seubert
Carolin
C
Götz
Andreas
A
Tresch
Achim
A
van Rooijen
Nico
N
Oelschlaeger
Tobias A
TA
Hill
Philip J
PJ
Gentschev
Ivaylo
I
Szalay
Aladar A
AA
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*
D024322:Amino Acids, Aromatic