The Deadly Chytrid Fungus: A Story of an Emerging Pathogen

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Published in the journal: . PLoS Pathog 6(1): e32767. doi:10.1371/journal.ppat.1000550
Category: Pearls
doi: https://doi.org/10.1371/journal.ppat.1000550

Summary

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Emerging infectious diseases present a great challenge for the health of both humans and wildlife. The increasing prevalence of drug-resistant fungal pathogens in humans [1] and recent outbreaks of novel fungal pathogens in wildlife populations [2] underscore the need to better understand the origins and mechanisms of fungal pathogenicity. One of the most dramatic examples of fungal impacts on vertebrate populations is the effect of the amphibian disease chytridiomycosis, caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd).

Amphibians around the world are experiencing unprecedented population losses and local extinctions [3]. While there are multiple causes of amphibian declines, many catastrophic die-offs are attributed to Bd [4],[5]. The chytrid pathogen has been documented in hundreds of amphibian species, and reports of Bd's impact on additional species and in additional geographic regions are accumulating at an alarming rate (e.g., see http://www.spatialepidemiology.net/bd). Bd is a microbial, aquatic fungus with distinct life stages. The motile stage, called a zoospore, swims using a flagellum and initiates the colonization of frog skin. Within the host epidermal cells, a zoospore forms a spherical thallus, which matures and produces new zoospores by dividing asexually, renewing the cycle of infection when zoospores are released to the skin surface (Figure 1). Bd is considered an emerging pathogen, discovered and described only a decade ago [6],[7]. Despite intensive ecological study of Bd over the last decade, a number of unanswered questions remain. Here we summarize what has been recently learned about this lethal pathogen.

Life cycle of the pathogenic chytrid fungus <i>Batrachochytrium dendrobatidis</i>. — **Fig. 1. Life cycle of the pathogenic chytrid fungus *Batrachochytrium dendrobatidis*.**

How Is Bd Related to Other Fungi?

Bd is a member of a basal group of fungi, the Chytridiomycota, and is the only known member of its order (the Rhizophydiales) to parasitize vertebrates. Bd is phylogenetically distant from any of the other ∼1,000 chytrid species [8], and the lack of close relatives capable of parasitizing vertebrates suggests that Bd pathogenicity evolved relatively recently. Further, population genetic data on Bd isolates collected from different amphibian populations around the world suggest that Bd is a recently spread pathogen rather than being endemic with altered relationships with hosts due to environmental change [9],[10].

How Has Bd Spread around the World So Quickly?

Africa was initially proposed as the geographic origin because the earliest evidence of Bd is from skin samples from African clawed frogs (Xenopus laevis) collected in 1938. African clawed frogs were traded globally for decades (from the 1930s–1960s) for pregnancy assays in humans [11]. Although based on a small sample size, recent population genetic work shows reduced genetic diversity of isolates from African clawed frogs and, instead, high allelic diversity in North American isolates collected from bullfrogs (Rana catesbeiana) [10],[12]. Although additional genetic work is needed, these studies suggest that Bd's origin may not be in Africa. Anthropogenic spread of Bd is a plausible explanation for at least some introductions [11],[13]. Some amphibian species that are traded globally may serve as disease reservoirs because they can carry Bd infections without morbidity. A number of mysteries remain about how Bd has dispersed to and persisted in remote pristine environments where anthropogenic introduction is unlikely. If Bd can survive independently of amphibian hosts, it must use non-amphibian organic materials as nutrient resources. Although Bd DNA has been detected in water bodies [14] and on rocks [15], conclusive evidence of Bd persistence in the environment is lacking.

How Does Bd Kill Frogs?

In infected amphibians, Bd is found in the cells of the epidermis and pathological abnormalities include a thickening of the outer layer of skin [6]. Cutaneous fungal infections in other vertebrates are not typically lethal, but amphibian skin is unique because it is physiologically active, tightly regulating the exchange of respiratory gases, water, and electrolytes. Thus, the physiological importance of the skin makes amphibians particularly vulnerable to skin infections. It has been hypothesized that Bd disrupts normal regulatory functioning of frog skin, and evidence suggests that electrolyte depletion and osmotic imbalance that occurs in amphibians with severe chytridiomycosis are sufficient to cause mortality [16],[17].

What Factors Are Implicated in Bd Pathogenicity/Virulence?

The molecular factors influencing Bd pathogenicity and virulence have yet to be conclusively identified. Some evidence suggests that Bd enzymatic activity directly influences pathogenesis. The initial penetration of Bd into amphibian epidermal cells likely requires digestive enzymes. In culture, Bd secretes extracellular proteases that degrade casein and gelatin [18],[19]. At the molecular level, genomic research into Bd is revealing intriguing expression patterns in genes such as those for serine protease and fungalysin metallopeptidase [20], two gene families involved in pathogenesis in other fungal pathogens. Full genomes of two Bd isolates have recently been sequenced, providing new resources for the study of molecular mechanisms of pathogenicity [21].

Are There Differences in Bd Isolate Virulence?

Several studies have shown variation in virulence among Bd isolates. In experimental infections, differences in frog survival have been observed when exposed to different Bd isolates (e.g., [22],[23]). Initial proteomic work suggests that Bd isolates differ in their proteome profiles [23]. However, controlled infection experiments with reciprocal host isolate treatments and paired genomic and proteomic studies are necessary to identify the functional determinants of Bd virulence.

Do All Frogs Respond Similarly to Bd?

Species, populations, and individuals vary widely in susceptibility to chytridiomycosis. Mortality rates in laboratory infection experiments can range from 0% to 100%, depending on the species (e.g., [22],[24]), age of animals [25], and temperature regime [26]. In the wild, some species and populations are extirpated while others, those that survive initial declines, persist with various levels of infection (e.g., [27],[28]). While the disease dynamics are undoubtedly influenced by local environmental conditions, particularly temperature, inherent differences in host susceptibility and behavior are also important. Colonization by Bd and subsequent disease development may be influenced by host defense mechanisms, such as secretions of antimicrobial peptides [29] or bacterial commensals with anti-fungal properties [30]. Some species-specific behavioral characteristics such as microhabitat selection, basking, aggregating in retreat sites, or association with water bodies may also affect the likelihood of infection and disease [31],[32].

How Can We Stem the Tide of Bd-Related Declines?

Despite many gaps in our understanding of chytridiomycosis, we are beginning to unravel important elements of this lethal disease and make progress towards amphibian conservation. Multiple conservation strategies have been proposed and are currently being implemented to mitigate the threat of chytridiomycosis. These plans include efforts to limit the spread of the disease, invest in captive breeding programs for highly vulnerable amphibians, and advance basic disease research. Continued research on the biology of both the host and the pathogen is necessary, and efforts to catalog and preserve the Bd isolates for ongoing research are particularly important (see http://www.spatialepidemiology.net/bd/ and http://www.bdbank.org/, [33]). The conservation challenges we face with chytridiomycosis—and other emerging pathogens—are best confronted by increasing our knowledge of disease processes from both host and pathogen perspectives.

Zdroje

1. WarnockDW

2006 Fungal diseases: an evolving public health challenge. Med Mycol 44 697 705

2. BlehertDS

HicksAC

BehrM

MeteyerCU

Berlowski-ZierBM

2009 Bat white-nose syndrome: an emerging fungal pathogen? Science 323 227 227

3. StuartSN

ChansonJS

CoxNA

YoungBE

RodriguesASL

2004 Status and trends of amphibian declines and extinctions worldwide. Science 306 1783 1786

4. LipsKR

BremF

BrenesR

ReeveJD

AlfordRA

2006 Emerging infectious disease and the loss of biodiversity in a Neotropical amphibian community. Proc Natl Acad Sci U S A 103 3165 3170

5. SchloegelL

HeroJM

BergerL

SpeareR

McDonaldKR

2006 The decline of the sharp-snouted day frog (Taudactylus acutirostris): the first documented case of extinction by infection in a free-ranging wildlife species? EcoHealth 3 35 40

6. BergerL

SpeareR

DaszakP

GreenDE

CunninghamAA

1998 Chytridiomycosis causes amphibian mortality associated with population declines in the rain forests of Australia and Central America. Proc Natl Acad Sci U S A 95 9031 9036

7. LongcoreJE

PessierAP

NicholsDK

1999 Batrachochytrium dendrobatidis gen et sp nov, a chytrid pathogenic to amphibians. Mycologia 91 219 227

8. JamesTY

LetcherPM

LongcoreJE

Mozley-StandridgeSE

PorterD

2006 A molecular phylogeny of the flagellated fungi (Chytridiomycota) and description of a new phylum (Blastocladiomycota). Mycologia 98 860 871

9. MorehouseEA

JamesTY

GanleyARD

VilgalysR

BergerL

2003 Multilocus sequence typing suggests the chytrid pathogen of amphibians is a recently emerged clone. Mol Ecol 12 395 403

10. JamesTY

LitvintsevaAP

VilgalysR

MorganJAT

TaylorJW

2009 Rapid global expansion of the fungal disease chytridiomycosis into declining and healthy amphibian populations. PLoS Pathog e1000458 doi:10.1371/journal.ppat.1000458

11. WeldonC

du PreezLH

HyattAD

MullerR

SpeareR

2004 Origin of the amphibian chytrid fungus. Emerg Infect Dis 10 2100 2105

12. GokaK

YokoyamaJ

UneY

KurokiT

SuzukiK

NakaharaM

KobayashiA

InabaS

MizutaniT

HyattAD

2009 Amphibian chytridiomycosis in Japan: distribution, haplotypes and possible route of entry into Japan. Molecular Ecology 18 4757 4774

13. FisherMC

GarnerTWJ

2007 The relationship between the emergence of Batrachochytrium dendrobatidis, the international trade in amphibians and introduced amphibian species. Fungal Biol Rev 21 2 9

14. KirshteinJD

AndersonCW

WoodJS

LongcoreJE

VoytekMA

2007 Quantitative PCR detection of Batrachochytrium dendrobatidis DNA from sediments and water. Dis Aquat Org 77 11 15

15. WalkerSF

SalasMB

JenkinsD

GarnerTWJ

CunninghamAA

2007 Environmental detection of Batrachochytrium dendrobatidis in a temperate climate. Dis Aquat Org 77 105 112

16. VoylesJ

BergerL

YoungS

SpeareR

WebbR

2007 Electrolyte depletion and osmotic imbalance in amphibians with chytridiomycosis. Dis Aquat Org 77 113 118

17. VoylesJ

YoungS

BergerL

CampbellC

VoylesWF

DinudomA

Cook

WebbR

AlfordRA

SkerrattLF

SpeareR

2009 Pathogenesis of chytridiomycosis, a cause of catastrophic amphibian declines. Science 326 582 585

18. PiotrowskiJS

AnnisSL

LongcoreJE

2004 Physiology of Batrachochytrium dendrobatidis, a chytrid pathogen of amphibians. Mycologia 96 9 15

19. SymondsEP

TrottDJ

BirdPS

MillsP

2008 Growth characteristics and enzyme activity in Batrachochytrium dendrobatidis isolates. Mycopathologia 166 143 147

20. RosenblumEB

StajichJE

MaddoxN

EisenMB

2008 Global gene expression profiles for life stages of the deadly amphibian pathogen Batrachochytrium dendrobatidis. Proc Natl Acad Sci U S A 105 17034 17039

21. RosenblumEB

FisherMC

JamesTY

StajichJE

LongcoreJE

GentryLR

PoortenTJ

2009 A molecular perspective: biology of the emerging pathogen Batrachochytrium dendrobatidis. Dis Aquat Org doi:10.3354/dao02179

22. BergerL

MarantelliG

SkerrattLL

SpeareR

2005 Virulence of the amphibian chytrid fungus Batrachochytrium dendrobatidis varies with the strain. Dis Aquat Org 68 47 50

23. FisherMC

BoschJ

YinZ

SteadDA

WalkerJ

2009 Proteomic and phenotypic profiling of the amphibian pathogen Batrachochytrium dendrobatidis shows that genotype is linked to virulence. Mol Ecol 18 415 429

24. DaszakP

StriebyA

CunninghamAA

LongcoreJE

BrownCC

2004 Experimental evidence that the bullfrog (Rana catesbeiana) is a potential carrier of chytridiomycosis, an emerging fungal disease of amphibians. Herpetolog J 14 201 207

25. LamirandeEW

NicholsDK

2002 Effects of host age on susceptibility to cutaneous chytridiomycosis in blue-and-yellow poison dart frogs (Dendrobates tinctorius). St. Paul, Minnesota. 3 13 In Proceedings of the Sixth International Symposium on the Pathology of Reptiles and Amphibians, 18–19 April 2001

26. WoodhamsDC

AlfordRA

MarantelliG

2003 Emerging disease of amphibians cured by elevated body temperature. Dis Aquat Org 55 65 67

27. RetallickRWR

McCallumH

SpeareR

2004 Endemic infection of the amphibian chytrid fungus in a frog community post-decline. PLoS Biol 2 e351 doi:10.1371/journal.pbio.0020351

28. BriggsCJ

VredenburgVT

KnappRA

RachowiczLJ