Transmission of a common intestinal neoplasm in zebrafish by cohabitation

Abstract

Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water. Intestinal lesions were observed in recipient fish in all exposure groups, including transmissions from previous recipient fish, and moribund fish exhibited a higher prevalence of neoplasms. We found a single 16S rRNA sequence, most similar to Mycoplasma penetrans, to be highly enriched in the donors and exposed recipients compared to unexposed control fish. We further tracked the presence of the Mycoplasma sp. using a targeted PCR test on individual dissected intestines or faeces or tank faeces. Original donor and exposed fish populations were positive for Mycoplasma, while corresponding unexposed control fish were negative. This study indicates an infectious aetiology for these transmissible tumours of zebrafish and suggests a possible candidate agent of a Mycoplasma species.

Retrospective analysis of the Zebrafish International Resource Center diagnostic data links Pseudocapillaria tomentosa to intestinal neoplasms in zebrafish Danio rerio (Hamilton 1822)

“…With our present study with zebrafish, the occurrence of the intestinal neoplasms in many cases and facilities in which the worms were absent shows that, while strongly linked, the presence of the worm is not required to develop these lesions. This agrees with laboratory transmission experiments in which the intestinal neoplasms were transmitted in the absence of the worms (Burns et al., 2018). The aetiology of neoplasia is often multifactorial, and whereas the P. tomentosa may not be the primary initiator, it is apparently an effective promoter following exposure to another agent, as the Mycoplasma sp.…”

“…Pseudocapillaria tomentosa penetrates the epithelium and causes severe, chronic inflammation in both diagnostic cases (Murray & Peterson, 2015) and in experimental studies (Gaulke et al., 2019). This provides an explanation for the correlations seen in our retrospective study and the observation that that tumours developed within populations of fish with P. tomentosa after about 3 months exposure (Gaulke et al., 2019) versus about 9 months without the worms (Burns et al., 2018). It is possible that the nematode and the Mycoplasma sp.…”

“…Supporting this observation, Burns et al. (2018) showed that the neoplasms could readily be transmitted in the absence of the worm by water‐borne exposure after about 9 months, and the disease was associated with a specific bacterial strain related to Mycoplasma penetrans . Following that study, Gaulke et al.…”

A longitudinal assessment of host-microbe-parasite interactions resolves the zebrafish gut microbiome’s link to Pseudocapillaria tomentosa infection and pathology

“…based on examination of tissues from each intestine. Following our previous study [22], two broad categories, inflammation and hyperplastic changes, were scored in zebrafish intestines. A total histopathology score, which is the sum of the inflammation and hyperplasia scores, was also calculated.…”

Review of diseases and health management in zebrafish Danio rerio (Hamilton 1822) in research facilities

“…Indeed, our recent review of the ZIRC diagnostic case database revealed that the worm was present in only about one‐fourth of the facilities or cases in which intestinal neoplasia was diagnosed. Burns et al (2018) showed that some intestinal carcinomas are naturally transmitted by either co‐habitation with or exposure to effluent from affected fish. They also correlated neoplasms with the presence of a specific mycoplasma's 16S rDNA sequence that was close to M. penetrans .…”