The benefit of using zebrafish (Danio rerio) models as part of an integrative approach to improve human health is being realized by the scientific community, with 800 laboratories, supported by some 735 grants from NIH using this fish model. As with any animal model, infections can compromise research by causing high mortalities and subclinical infections compromise research by inducing non-protocol induced variation. Third, Mycobacterium spp. that have been reported from zebrafish are all recognized human pathogens, and thus fish with these infections present human health concerns. Therefore, as with other models, it is imperative to conduct studies with disease-free, healthy zebrafish. Based on 12 years of diagnostics performed by the Zebrafish International Research Center (ZIRC) and research conducted in the last cycles of this grant, we can conclude the following: Mycobacterium spp. and infections by Pseudoloma neurophilia (Microsporidia) are very common in zebrafish research laboratories. Some research facilities have experienced devastating mortalities in their zebrafish colonies due to infections by virulent Mycobacterium spp. Persistent, but less severe, infections by other mycobacteria and Pseudoloma have also plagued several facilities. The modes of transmission of these pathogens have been elucidated, and PCR-based diagnostic tests are available. However, little is known about how subclinical infections impact research endpoints, which is important now as several researchers are now using zebrafish as models in long-term studies on human pathogens, toxicology, aging and behavior. The major aim of the present study is to improve the health of zebrafish used in research facilities by investigating efficacy of disinfectants and antibiotics to reduce or eliminae infections. Evaluation of impacts of chronic infections by M. chelonae and Pseudoloma on fecundity, behavior, and cytokine profiles is another aim. Zebrafish that are immunsuppressed by gamma radiation are important models for human cancer studies, and investigate the impacts of underlying Pseudoloma infections in these fish will be studied. Results will be quickly distributed to the zebrafish community through through publications and the ZIRC web based manual on zebrafish.

Public Health Relevance

Zebrafish have become an extermely important model in biomedical research. Two diseases are very common in research facilities;mycobacteriosis and microsporidiosis caused by Pseudoloma neurophilia. This study investigates methods of control and elucidates the impacts of these infections in this fish. This will lead to reducation of these infections and associated non-protocol induced variation in resarch.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
3R24OD010998-11S1
Application #
8721085
Study Section
Special Emphasis Panel (ZOD1-CM-6 (01))
Program Officer
Chang, Michael
Project Start
2003-07-01
Project End
2017-05-31
Budget Start
2013-09-01
Budget End
2014-05-31
Support Year
11
Fiscal Year
2013
Total Cost
$36,500
Indirect Cost
$11,500
Name
Oregon State University
Department
Microbiology/Immun/Virology
Type
Schools of Earth Sciences/Natur
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339
Chang, C T; Doerr, K M; Whipps, C M (2017) Antibiotic treatment of zebrafish mycobacteriosis: tolerance and efficacy of treatments with tigecycline and clarithromycin. J Fish Dis 40:1473-1485
Meritet, Danielle M; Mulrooney, Donna M; Kent, Michael L et al. (2017) Development of Quantitative Real-Time PCR Assays for Postmortem Detection of Mycobacterium spp. Common in Zebrafish (Danio rerio) Research Colonies. J Am Assoc Lab Anim Sci 56:131-141
Ndikumana, Steve; Pelin, Adrian; Williot, Alexandre et al. (2017) Genome Analysis of Pseudoloma neurophilia: A Microsporidian Parasite of Zebrafish (Danio rerio). J Eukaryot Microbiol 64:18-30
Martins, M L; Watral, V; Rodrigues-Soares, J P et al. (2017) A method for collecting eggs of Pseudocapillaria tomentosa (Nematoda: Capillariidae) from zebrafish Danio rerio and efficacy of heat and chlorine for killing the nematode's eggs. J Fish Dis 40:169-182
Spagnoli, S; Sanders, J; Kent, M L (2017) The common neural parasite Pseudoloma neurophilia causes altered shoaling behaviour in adult laboratory zebrafish (Danio rerio) and its implications for neurobehavioural research. J Fish Dis 40:443-446
Wilson, Alexandria K; Watral, Virginia G; Kent, Michael L et al. (2017) Draft Genome Sequence of Pseudomonas sp. Strain DrBHI1 (Phylum Proteobacteria). Genome Announc 5:
Burns, A R; Watral, V; Sichel, S et al. (2017) Transmission of a common intestinal neoplasm in zebrafish by cohabitation. J Fish Dis :
Mason, Timothy; Snell, Kathy; Mittge, Erika et al. (2016) Strategies to Mitigate a Mycobacterium marinum Outbreak in a Zebrafish Research Facility. Zebrafish 13 Suppl 1:S77-87
Spagnoli, Sean T; Sanders, Justin L; Watral, Virginia et al. (2016) Pseudoloma neurophilia Infection Combined with Gamma Irradiation Causes Increased Mortality in Adult Zebrafish (Danio rerio) Compared to Infection or Irradiation Alone: New Implications for Studies Involving Immunosuppression. Zebrafish 13 Suppl 1:S107-14
Kent, Michael L; Watral, Virginia G; Kirchoff, Nicole S et al. (2016) Effects of Subclinical Mycobacterium chelonae Infections on Fecundity and Embryo Survival in Zebrafish. Zebrafish 13 Suppl 1:S88-95

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