Emerging infectious diseases are a threat to human and wildlife populations, and there is an urgent need to identify the ecological principles that are associated with disease dynamics.  Diseases have typically been approached from a biomedical perspective, such as identification of the pathogen, vaccine development and vaccination.  This approach is less effective when the ecological context of the disease is complex, e.g., when the pathogen affects multiple host species.  Another critical ecological context is the interaction between the pathogen and resident microbes on or in host individuals.  An understanding of the role that beneficial microbes play in controlling pathogens is increasingly recognized as vital in order to maintain health and control disease outbreaks in a variety of species, including humans.  It is, thus, important to understand the community ecology of beneficial microbes.

Amphibian skin is attacked by a fungal pathogen, Batrachochytrium dendrobatidis, which is a chytrid fungus that causes chytridiomycosis.  This disease has caused widespread population declines and apparent extinctions in many areas of the world, such as Australia and the Americas.  Our hypothesis is that study of the ecological context of emerging infectious diseases, such as chytridiomycosis, is crucial in understanding and eventually controlling the disease. The ecological context of interest is the interaction of epibiotic bacterial communities and colonizing zoospores of the pathogen.  We further hypothesize that resident microbial communities can prevent or limit the negative effects of chytridiomycosis by production of anti-chytrid metabolites.

Our research is investigating how beneficial microbes are and can be transmitted to amphibian skins and is elucidating the mechanisms of protection by characterizing amphibians’ cutaneous microbes and their antifungal metabolites.  We have developed  methods to non-destructively sample amphibians’ antifungal metabolites that are produced by their bacterial communities.  This technique allows us to correlate antifungal metabolite “fingerprints” of bacterial communities with disease outcome in individuals and in populations.  Our work can help explain why some amphibian species are unaffected by chytridiomycosis while others are greatly negatively affected.  Fundamentally, we hope to uncover insights into the community ecology context of disease, specifically how a cutaneous ecosystem affects the health of an amphibian host.

Because chytridiomycosis is a major threat to global amphibian diversity, one anticipated outcome of our work is that a manipulation of amphibians’ cutaneous microbiota can halt epidemic outbreaks of this disease in nature and protect individuals in survival assurance colonies so that they can be re-introduced into nature.  The potential discovery of antifungal molecules opens the door to a novel chemotherapeutics that could be applicable not only to amphibian conservation but also to human medicine. 

At JMU, I collaborate with Dr. Kevin Minbiole, who is in the Department of Chemistry and Biochemistry.  Work in his laboratory has shown that antifungal metabolites found on amphibian skins and produced by amphibians’ skin microbes are often in high enough concentration to inhibit fungal zoospores.

I am collaborating with Dr. Lisa Belden at Virginia Tech on the role of beneficial microbes in preventing disease.

Our research is currently funded by the National Science Foundation and supported by the USDA Forest Service.

References

Becker, M.H., R.N. Harris, K.P.C. Minbiole, C.R. Schwantes*, L.A. Rollins-Smith, L.K. Reinert, R.M. Brucker, R.J. Domangue, B. Gratwicke. 2012. Towards a better understanding of the use of probiotics for preventing chytriodiomycosis in Panamanian golden frogs. EcoHealth, in press.

Muletz*, C.R., J.M. Myers, R.J. Domangue, J.B. Herrick, R.N. Harris. 2012. Soil bioaugmentation with amphibian cutaneous bacteria protects amphibian hosts from infection by Batrachochytrium dendrobatidis. Biological Conservation, accepted with minor revisions.

Woodhams, D.C., C.C. Geiger, L.K. Reinert, L.A. Rollins-Smith, B. Lam, R.N. Harris, C.J. Briggs, V.T. Vredenburg, J. Voyles. 2012. Treatment of amphibians infected with chytrid fungus: learning from failed treatments with itraconazole, antimicrobial peptides, bacteria, and heat therapy. Diseases of Aquatic Organisms 98:11-25.

Lam*, B. A., D. B. Walton, R. N. Harris. 2011. Motile zoospores of Batrachochytrium dendrobatidis move away from antifungal metabolites produced by amphibian skin bacteria. EcoHealth 8: 36-45.

Walke, J.B., R.N. Harris, L.K. Reinert, L.A. Rollins-Smith, D. C. Woodhams. 2011. Social immunity in amphibians:  Evidence for vertical transmission of innate defenses. Biotropica, in press.

Wiggins*, P. J., J. M. Smith*, R. N. Harris, K.P.C. Minbiole.  2011. The gut of red-backed salamanders (Plethodon cinereus) may serve as a reservoir for an antifungal cutaneous bacterium.  Journal of Herpetology, in press.

Vredenburg, V.T., C. J. Briggs, R. N. Harris. 2011. Host-pathogen dynamics of amphibian chytridiomycosis:  the role of the skin microbiome in health and disease. In Fungal Diseases: An Emerging Challenge to Human, Animal, and Plant Health. Editors: Olsen, L., E. Choffnes, D. A. Relman, L. Pray. Washington, D.C.: The National Academies Press, pp. 342 -355.

Becker*, M. H., R. N. Harris. 2010. Cutaneous bacteria of the redback salamander prevent morbidity associated with a lethal disease. PLoS One PLoS ONE 5(6): e10957. doi:10.1371/journal.pone.0010957

Lam*, B. A., J. B. Walke, V. T. Vredenburg, R. N. Harris. 2010. Proportion of individuals with anti-Batrachochytrium dendrobatidis skin bacteria is associated with population persistence in the frog Rana muscosa. Biological Conservation 143: 529–531.

Becker, M. H., R. M. Brucker, C. R. Schwantes, R. N. Harris, K.P.C. Minbiole. 2009. The bacterially-produced metabolite violacein is associated with survival in amphibians infected with a lethal disease. Applied and Environmental Microbiology 75:6635-6638.

Harris, R. N., R. M. Brucker, J. B. Walke, M. H. Becker, C. R. Schwantes*, D. C Flaherty*, B. A. Lam, D. C. Woodhams, C. J. Briggs, V. T. Vredenburg, K. P. C. Minbiole.  2009. Skin microbes on frogs prevent morbidity and mortality caused by a lethal skin fungus. ISME Journal 3:818-824.

Harris, R. N., A. Lauer, M. A. Simon, J. L. Banning*, R. A. Alford.  2009. Addition of antifungal skin bacteria to salamanders ameliorates the effects of chytridiomycosis. Diseases of Aquatic Organisms 83:11-16.

Banning*, J. L., A. L. Weddle*, G. W. Wahl III*, M. A. Simon, A. Lauer, R. L. Walters*, and R. N. Harris. 2008. Antifungal skin bacteria, embryonic survival, and communal nesting in four-toed salamanders, Hemidactylium scutatum. Oecologia 156:423–429

Brucker*, R. M., C. M. Baylor*, R. L. Walters*, A. Lauer, R. N. Harris, and K. P. C. Minbiole. 2008. The identification of 2,4-diacetylphloroglucinol as an antifungal metabolite produced by cutaneous bacteria of the salamander Plethodon cinereus. Journal of Chemical Ecology 34:39-43.

Brucker*, R. M., R. N. Harris, C. R. Schwantes*, T. N. Gallaher, D. C. Flaherty*, B. A. Lam*, K. P. C. Minbiole. 2008. Amphibian chemical defense: antifungal metabolites of the microsymbiont Janthinobacterium lividum on the salamander Plethodon cinereus. Journal of Chemical Ecology 34:1422-1429.

Lauer, A., M. A. Simon, J. L. Banning*, B. Lam*, and R. N. Harris. 2008. Diversity of cutaneous bacteria with antifungal activity isolated from female four-toed salamanders.  The ISME Journal 2: 145–157.

Belden, L. K., and R. N. Harris. 2007. Infectious diseases in wildlife:  the community ecology context. Frontiers in Ecology and Environment 5:533-539.

Lauer, A., M. A. Simon, J. L. Banning*, E. André*, K. Duncan*, and R.  N. Harris.  2007. Common cutaneous bacteria from the eastern red-backed salamander can inhibit pathogenic fungi. Copeia, 2007: 630-640.

Woodhams, D. C., V. T. Vredenburg, M. J. Stice, M. A. Simon, D. Billheimer, B. Shakhtour, Y. Shyr, C. J. Briggs, L. A. Rollins-Smith, and R. N. Harris. 2007. Symbiotic bacteria contribute to innate immune defenses of the threatened mountain yellow-legged frog, Rana muscosa.  Biological Conservation, 138: 390-398.

Woodhams, D. C., L. A. Rollins-Smith, R. A. Alford, M. A. Simon & R. N. Harris. 2007. Response - Innate immune defenses of amphibian skin: antimicrobial peptides and more. Animal Conservation 10: 425–428

Harris, R. N., T. Y. James, A. Lauer, M. A. Simon, A. Patel*. 2006. The amphibian pathogen Batrachochytrium dendrobatidis is inhibited by the cutaneous bacteria of amphibian species.  EcoHealth 3:53-56.

*undergraduate or masters student co-author