Murine solid tumours as a novel model to study bacterial biofilm formation in vivo

Abstract

Bacteria of many species are able to invade and colonize solid tumours in mice. We have focused on Salmonella enterica serovar Typhimurium. Detailed analysis revealed that such tumour‐invading Salmonella form biofilms, thus providing a versatile in vivo test system for studying bacterial phenotypes and host–pathogen interactions. It appears that biofilm formation by S. typhimurium is induced as a defence against the immune system of the host, and in particular against neutrophils. Further, we extended our work to the clinically more relevant biofilm infection by Pseudomonas aeruginosa. The induction of P. aeruginosa biofilms in neoplastic tissue appears to be elicited as a reaction against the immune system. Reconstitution experiments reveal that T cells are responsible for biofilm induction. Isogenic mutants that are no longer able to form biofilms can be used for comparison studies to determine antimicrobial resistance, especially therapeutic efficacy against P. aeruginosa located in biofilms.

In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa

“…It employs transplantable solid tumors in mice that are preferentially colonized by P. aeruginosa as well as by other bacteria after systemic administration (18). The microenvironment of the colonized tumor leads to biofilm formation by the bacteria (18)(19)(20). Apparently, this microenvironment of the murine tumor resembles very closely that found in the CF lung or in burn wounds (21).…”

“…We have recently described a model that might accomplish the requirements. It employs transplantable solid tumors in mice that are preferentially colonized by P. aeruginosa as well as by other bacteria after systemic administration (18). The microenvironment of the colonized tumor leads to biofilm formation by the bacteria (18)(19)(20).…”

Contribution of Veillonella parvula to Pseudomonas aeruginosa-Mediated Pathogenicity in a Murine Tumor Model System

“…As observed before for the facultative anaerobes (31) and P. aeruginosa (30,32), V. parvula accumulated in the tumor tissue. However, accumulation of V. parvula was only detected when sufficient numbers of bacteria were intravenously administered (2 ϫ 10 8 CFU).…”

“…It has previously been shown that facultative anaerobic bacteria, such as Salmonella Typhimurium and Escherichia coli, are able to colonize solid subcutaneous tumors of the colon carcinoma cell line CT26 in a mouse tumor model (50). We have further demonstrated that P. aeruginosa, although rapidly cleared from the blood and other organs, is also able to gather and multiply specifically in the murine tumor tissue following intravenous administration (31,32). Of note, whereas facultative anaerobic bacteria like Salmonella colonize the whole tumor tissue, including the anaerobic center, the nonfermenter P. aeruginosa colonized mainly the outer rim of the tumor tissue.…”

“…Most bacteria are able to invade and colonize such tumors. In addition, we could show that Salmonella enterica serovar Typhimurium, as well as P. aeruginosa, forms biofilms in this neoplastic tissue (32). Transcriptional profiling of tumor-colonizing P. aeruginosa revealed that the microenvironment encountered by the bacteria in the tumor closely resembles the microenvironment of the CF lung (33).…”