Abstract
BACKGROUND: The anticancer drugs, such as DNA replication inhibitors, stimulate bacterial adhesion and induce the bacterial SOS response. As a variety of bacterial mutants can be generated during SOS, novel phenotypes are likely to be selected under the drug pressure. PRESENTATION OF THE HYPOTHESIS: Bacteria growing with cancer cells in the presence of the replication inhibitors undergo the SOS response and evolve advantageous phenotypes for the bacteria to invade the cancer cells in order to evade the drug attack. This hypothesis predicts that bacteria produce the proteins that mediate bacterial capture and invasion of cancer cells--the advantageous phenotypes. Generation of the phenotypes may be facilitated during the SOS response induced by anticancer drugs. EXPERIMENTAL DESIGN: 1) Examine attachment and invasion of bacterium Pseudomonas aeruginosa and the SOS mutant control to cancer cells in the presence of the anticancer drugs that inhibit DNA replication enzymes and trigger the SOS response. 2) Reveal the bacterial proteins that exhibit changes in expression. 3) Identify the genes encoding cancer adhesion and invasion. 4) Construct the mutants for the genes, clone and express these genes. 5) Examine the bacterial capture and invasion of cancer cells in contrast to non-cancer control. EXPECTED RESULTS: 1) The bacterial proteins will be differentially induced during bacteria-cancer interaction under the SOS response to the anticancer drugs. 2) Knocking out the bacterial cancer-adhesion-invasion genes will disrupt the adhesion-invasion phenotypes of the bacteria. 3) Expressing these genes will direct the bacterial capture and invasion of cancer cells. IMPLICATIONS OF THE HYPOTHESIS: Bacteria can evolve anticancer phenotypes targeting metastatic cells. If this hypothesis is true, the outcomes will contribute to development of a novel bacterial anti-metastasis regimen.