Abstract

Emerging fungal pathogens pose a greater threat to biodiversity than any other parasitic group1, causing declines of many taxa, including bats, corals, bees, snakes and amphibians1,2,3,4. Currently, there is little evidence that wild animals can acquire resistance to these pathogens5. Batrachochytrium dendrobatidis is a pathogenic fungus implicated in the recent global decline of amphibians6. Here we demonstrate that three species of amphibians can acquire behavioural or immunological resistance to B. dendrobatidis. Frogs learned to avoid the fungus after just one B. dendrobatidis exposure and temperature-induced clearance. In subsequent experiments in which B. dendrobatidis avoidance was prevented, the number of previous exposures was a negative predictor of B. dendrobatidis burden on frogs and B. dendrobatidis-induced mortality, and was a positive predictor of lymphocyte abundance and proliferation. These results suggest that amphibians can acquire immunity to B. dendrobatidis that overcomes pathogen-induced immunosuppression7,8,9 and increases their survival. Importantly, exposure to dead fungus induced a similar magnitude of acquired resistance as exposure to live fungus. Exposure of frogs to B. dendrobatidis antigens might offer a practical way to protect pathogen-naive amphibians and facilitate the reintroduction of amphibians to locations in the wild where B. dendrobatidis persists. Moreover, given the conserved nature of vertebrate immune responses to fungi5 and the fact that many animals are capable of learning to avoid natural enemies10, these results offer hope that other wild animal taxa threatened by invasive fungi might be rescued by management approaches based on herd immunity.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    et al. Emerging fungal threats to animal, plant and ecosystem health. Nature 484, 186–194 (2012)

  2. 2.

    et al. Bat white-nose syndrome: an emerging fungal pathogen? Science 323, 227 (2009)

  3. 3.

    et al. Patterns of widespread decline in North American bumble bees. Proc. Natl Acad. Sci. USA 108, 662–667 (2011)

  4. 4.

    et al. Chrysosporium sp. infection in eastern massasauga rattlesnakes. Emerg. Infect. Dis. 17, 2383–2384 (2011)

  5. 5.

    & Parallels in fungal pathogenesis on plant and animal hosts. Eukaryot. Cell 5, 1941–1949 (2006)

  6. 6.

    et al. Status and trends of amphibian declines and extinctions worldwide. Science 306, 1783–1786 (2004)

  7. 7.

    et al. The invasive chytrid fungus of amphibians paralyzes lymphocyte responses. Science 342, 366–369 (2013)

  8. 8.

    et al. Genome-wide transcriptional response of Silurana (Xenopus) tropicalis to infection with the deadly chytrid fungus. PLoS ONE 4, e6494 (2009)

  9. 9.

    et al. Expression profiling the temperature-dependent amphibian response to infection by Batrachochytrium dendrobatidis. PLoS ONE 4, e8408 (2009)

  10. 10.

    & Chemical alarm signalling in aquatic predator-prey systems: A review and prospectus. Ecoscience 5, 338–352 (1998)

  11. 11.

    & Systemic acquired resistance. Annu. Rev. Phytopathol. 42, 185–209 (2004)

  12. 12.

    et al. Mitigating amphibian disease: strategies to maintain wild populations and control chytridiomycosis. Front. Zool. 8, 8 (2011)

  13. 13.

    , & Enzootic and epizootic dynamics of the chytrid fungal pathogen of amphibians. Proc. Natl Acad. Sci. USA 107, 9695–9700 (2010)

  14. 14.

    , , & Confronting inconsistencies in the amphibian-chytridiomycosis system: implications for disease management. Biol. Rev. Camb. Philos. Soc. 89, 477–483 (2014)

  15. 15.

    , , & Toward immunogenetic studies of amphibian chytridiomycosis: linking innate and acquired immunity. Bioscience 59, 311–320 (2009)

  16. 16.

    , , , & Amphibian immune defenses against chytridiomycosis: impacts of changing environments. Integr. Comp. Biol. 51, 552–562 (2011)

  17. 17.

    , , , & Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the south african clawed frog, Xenopus laevis. Infect. Immun. 78, 3981–3992 (2010)

  18. 18.

    & MHC genotypes associate with resistance to a frog-killing fungus. Proc. Natl Acad. Sci. USA 108, 16705–16710 (2011)

  19. 19.

    , & Temperature, hydric environment, and prior pathogen exposure alter the experimental severity of chytridiomycosis in boreal toads. Dis. Aquat. Organ. 95, 31–42 (2011)

  20. 20.

    et al. Prior infection does not improve survival against the amphibian disease chytridiomycosis. PLoS ONE 8, e56747 (2013)

  21. 21.

    & Immunization is ineffective at preventing infection and mortality due to the amphibian chytrid fungus Batrachochytrium dendrobatidis. J. Wildl. Dis. 46, 70–77 (2010)

  22. 22.

    et al. Experimental infection of self-cured Leiopelma archeyi with the amphibian chytrid Batrachochytrium dendrobatidis. Dis. Aquat. Organ. 92, 159–163 (2010)

  23. 23.

    , , & Parasites, info-disruption, and the ecology of fear. Oecologia 159, 447–454 (2009)

  24. 24.

    , , & Behavioral reduction of infection risk. Proc. Natl Acad. Sci. USA 96, 9165–9168 (1999)

  25. 25.

    , & During frog ontogeny, PHA and Con-A responsiveness of splenocytes precedes that of thymocytes. Immunology 52, 491–500 (1984)

  26. 26.

    et al. Immune defenses of Xenopus laevis against Batrachochytrium dendrobatidis. Front. Biosci. S1, 68–91 (2009)

  27. 27.

    , , , & Comparison of the immunosuppressive activities of the antimycotic agents, intraconazole, fluconazole, ketoconazole and miconazole on human T-cells. Int. J. Immunopharmacol. 13, 299–304 (1991)

  28. 28.

    , , , & Selecting for tolerance against pathogens and herbivores to enhance success of reintroduction and translocation. Conserv. Biol. 26, 586–592 (2012)

  29. 29.

    et al. Chytrid fungus Batrachochytrium dendrobatidis has nonamphibian hosts and releases chemicals that cause pathology in the absence of infection. Proc. Natl Acad. Sci. USA 110, 210–215 (2013)

  30. 30.

    et al. Diagnostic assays and sampling protocols for the detection of Batrachochytrium dendrobatidis. Dis. Aquat. Organ. 73, 175–192 (2007)

Download references

Acknowledgements

We thank W. Holden and J. Pask for their assistance with the immunological assays, J. Cohen for comments on the manuscript, and our undergraduate assistants H. Folse, S. Lopez, L. Soto, S. Hekkanen and E. Creasey. We also thank V. Vasquez and J. Longcore for providing the Bd isolates used in these experiments. Funds were provided by grants from the National Science Foundation (DEB 0516227 and EF-1241889 to J.R.R. and IOS-1121758 to L.A.R.-S.), the National Institutes of Health (R01GM109499 to J.R.R.), the US Department of Agriculture (NRI 2006-01370 and 2009-35102-0543 to J.R.R.), the US Environmental Protection Agency grant (STAR R83-3835 and CAREER 83518801 to J.R.R.), and the NSF RCN “Refining and Diversifying Ecoimmunology”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

    • Taegan A. McMahon
    •  & Jason R. Rohr

    These authors contributed equally to this work.

Affiliations

  1. University of South Florida, Department of Integrative Biology, Tampa, Florida 33620, USA

    • Taegan A. McMahon
    • , Brittany F. Sears
    • , Scott M. Bessler
    • , Jenise M. Brown
    • , Kaitlin Deutsch
    • , Neal T. Halstead
    • , Garrett Lentz
    • , Nadia Tenouri
    • , Suzanne Young
    • , David J. Civitello
    • , Nicole Ortega
    •  & Jason R. Rohr
  2. University of Tampa, Department of Biology, Tampa, Florida 33606, USA

    • Taegan A. McMahon
  3. Allegheny College, Department of Biology, Meadville, Pennsylvania 16335, USA

    • Matthew D. Venesky
  4. Vanderbilt University, Biological Sciences Department, Nashville, Tennessee 37232, USA

    • J. Scott Fites
    •  & Louise A. Rollins-Smith
  5. Vanderbilt University, School of Medicine, Departments of Pathology, Microbiology and Immunology and Pediatrics, Nashville, Tennessee 37232, USA

    • Laura K. Reinert
    •  & Louise A. Rollins-Smith
  6. Oakland University, Department of Biology, Rochester, Michigan 48309, USA

    • Thomas R. Raffel

Authors

  1. Search for Taegan A. McMahon in:

  2. Search for Brittany F. Sears in:

  3. Search for Matthew D. Venesky in:

  4. Search for Scott M. Bessler in:

  5. Search for Jenise M. Brown in:

  6. Search for Kaitlin Deutsch in:

  7. Search for Neal T. Halstead in:

  8. Search for Garrett Lentz in:

  9. Search for Nadia Tenouri in:

  10. Search for Suzanne Young in:

  11. Search for David J. Civitello in:

  12. Search for Nicole Ortega in:

  13. Search for J. Scott Fites in:

  14. Search for Laura K. Reinert in:

  15. Search for Louise A. Rollins-Smith in:

  16. Search for Thomas R. Raffel in:

  17. Search for Jason R. Rohr in:

Contributions

T.A.M., T.R.R., J.R.R., B.F.S., N.T.H. and J.M.B. conceived and designed the first immunological resistance experiment, T.A.M., J.R.R., B.F.S., S.M.B., N.T.H., N.O. and J.M.B conceived and designed the second immunological resistance experiment, M.D.V. and J.R.R. conceived and designed the behavioural resistance experiment. T.A.M. directed the first and second immunological resistance experiments and M.D.V. directed the behavioural resistance experiments. T.A.M., B.F.S., S.M.B., N.T.H., J.M.B., G.L., N.T., S.Y. and M.D.V. conducted the first and second immunological resistance experiments; M.D.V. and K.D. conducted the behavioural resistance experiments, and T.A.M., L.K.R., J.S.F. and L.A.R.-S. conducted the antimicrobial peptide collection and lymphocyte assays. T.A.M. and J.R.R. conducted the statistical analyses for the first and second immunological resistance experiments and D.J.C. consulted on these analyses; M.D.V. and J.R.R. conducted the statistical analyses for the behavioural resistance experiment. J.R.R. wrote the manuscript and handled all submissions and revisions. T.A.M. and B.F.S. wrote parts of the methods, and all authors contributed to its editing.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Taegan A. McMahon or Jason R. Rohr.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Methods, Supplementary Results, a Supplementary Discussion and additional references.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature13491

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.