Abstract 4987: Biofilm-producing sulfate-reducing bacteria suppress tumor burden in a rat model of colon cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 78; no. 13_Supplement; p. 4987
• Main Authors: Busi, Susheel Bhanu, Leon, Kara B. De, Wall, Judy D., Amos-Landgraf, James M.
• Format: Journal Article
• Language: English
• Published: 01-07-2018
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-4987

Human epidemiological and animal model studies have shown that the presence of colon cancer is associated with certain microbiota. Previously, we re-derived genetically identical embryos of the Pirc (F344/NTac-Apc+/Pirc) rat model of familial adenomatous polyposis using three strains of surrogate dams (F344/NHsd, LEW/SsNHsd, and Crl:SD), each harboring distinct gut microbiota (GM) that modulated adenoma susceptibility. Bacterial relative abundances as determined by 16S rDNA sequencing showed several taxa correlating with suppression of both tumor growth and phenotype penetrance as early as 1 month of age. One taxon associated with reduced adenoma burden was a sulfate-reducing bacterium, viz. Desulfovibrio spp. To determine if Desulfovibrio was responsible for differences in tumor burden, Pirc rats harboring complex GM were gavaged at 14 and 15 days of age with two genetic isolates of Desulfovibrio (~10^8 colony forming units, CFU): biofilm-forming DvH-MT and biofilm-deficient DvH-MO. We found that the rats stably colonized with the biofilm-forming DvH-MT strain, with the bacteria present at 4 months of age. Adenoma burden at sacrifice showed that the biofilm-competent strain significantly reduced colonic adenoma size (t-test, p<0.05), compared to the biofilm-deficient, DvH-MO-treated rats.
To understand how the biofilm-forming capacity of the DvH-MT strain modulated adenoma burden, the genomes of the DvH-MT and DvH-MO strains were sequenced and 12 variants were identified between the two strains. In the DvH-MO strain one variant in the DVU1017 type-1 secretion system ABC transporter binding protein gene was shown to be required for biofilm-formation by Desulfovibrio in vitro. This gene was inactivated in the parent DvH-MT strain and the new construct was designated JWT716. To determine the presence and proximity of Desulfovibrio to adenomas in the colon, we modified the parental DvH-MT to express the fluorescent protein, dTomato and designated the fluorescent strain as JWT733. Pirc rats were treated with the biofilm-forming, JWT733 and the biofilm-deficient, JWT716.
3-months post-treatment we confirmed via qRT-PCR the presence of the biofilm-forming, JWT733 in fecal samples. JWT716 was undetectable in the fecal samples from most rats. Using a narrow-band filter to detect dTomato, we confirmed JWT733 colonization in the treated rats by colonoscopy. At 4 months of age, the rats were sacrificed and adenoma burden was estimated. We found that the biofilm-forming Desulfovibrio suppressed tumor burden in the colon compared to rats treated with the biofilm-deficient strain (t-test, p<0.05). This implicates the role of biofilm formation and potentially sulfate-reduction by this bacterium in the suppression of tumor multiplicity. In this model of colon cancer, Desulfovibrio alone or in concert may be residing in a niche in the intestinal mucus layer creating a beneficial or protective biofilm.
Citation Format: Susheel Bhanu Busi, Kara B. De Leon, Judy D. Wall, James M. Amos-Landgraf. Biofilm-producing sulfate-reducing bacteria suppress tumor burden in a rat model of colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4987.