Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2021

Bacteriophage FNU1 attenuates chemotherapy resistance and increased cell proliferation in gastric cancer cells and colon cancer cells co-cultured with Fusobacterium nucleatum (#40)

Mwila Kabwe 1 , Terri Meehan-Andrews 1 , Steve Petrovski 2 , Stuart Dashper 3 , Joseph Tucci 1
  1. Dept of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, Victoria, Australia
  2. Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, VIC, Australia
  3. Melbourne Dental School, University of Melbourne, Melbourne, Victoria, Australia

Fusobacterium nucleatum is a Gram-negative aerotolerant pathogen that has traditionally been associated with periodontal disease. We were the first group to isolate a lytic bacteriophage, FNU1, against this bacteria. Recent studies have shown F. nucleatum to be an onco-bacteria in promoting cancer progression and facilitating chemotherapy resistance. We designed co-culture systems whereby colon cancer cells and gastric cancer cells were grown with F. nucleatum. This allowed testing of the effectiveness of the antibiotic ampicillin and FNU1 in negating the effects of F. nucleatum on the cancer cells and their response to chemotherapy. Initially, we showed that when co-cultured with cancer cells, F. nucleatum was often closely associated with, and localised in and around the cancer cells. This was also associated with an increase in the proliferation of the cancer cells. When treated with ampicillin, cancer cell growth in the co-cultures was increased, unlike treatment with bacteriophage FNU1, which mitigated these proliferative effects. Further, cancer cells co-cultured with F. nucleatum showed resistance to oxaliplatin, while this resistance was overcome when treated with bacteriophage FNU1. We present here evidence supporting the capacity of bacteriophages to not only eliminate F. nucleatum in close association with cancer cells, but also significantly attenuate F. nucleatum induced cancer cell proliferation and chemotherapy resistance.