Wednesday, July 16, 2014

mBio: The Remarkable Evolution Of Cryptococcus Gatti


Credit CDC


# 8837



Although we normally think of viral or bacterial pathogens when we talk about infectious diseases, mycotic (fungal) diseases exert a heavy burden on human health as well.


A little over a year ago, in MMWR: Coccidioidomycosis Rising, we looked at dramatic increase in the number of Valley Fever infections over the past 13 years (1998-2011).


Coccidioidomycosisis – perhaps the best known fungal infection in North America – is caused by the inhalation of spores from one of two soil borne fungi - Coccidioides immitis or C. posadasii - both commonly found in the American Southwest.  Their spores can remain dormant in the desert soil for years, only to become airborne when the earth is disturbed by farming, earthquakes, construction, or windstorms.


Most of the people who live in regions where these fungi are endemic are eventually exposed and either develop brief asymptomatic infections or mild flu-like symptoms. 


But `Cocci’ isn’t alone, as another mycotic disease with a wide range in the United States is called Histoplasmosis, which can be found in the Ohio River Valley and along the lower Mississippi river. The causative agent is Histoplasma capsulatum, a fungus which is found in bird and bat droppings. Its spores can become airborne when these droppings dry out and are picked up by the wind. 


Credit Wikipedia

Another fungal threat is Blastomycosis (aka Gilchrist's disease), which is caused by Blastomyces dermatitidis, which is found in decaying leaves and grass.



While these mycotic diseases have long been endemic to North America, a new fungus arrived in the Pacific Northwest from the tropics roughly 15 years ago, and has not only adapted to a much colder environment, it has picked up virulence as well. 


It is called Cryptococcus gattii, and it showed up unexpectedly on Vancouver Island in 1999, and has since then has spread into Washington and Oregon.


In 2010 the CDC’s Journal of Emerging Infectious Diseases published a research article on spread spread of C. gattii  in British Columbia (see A Fungus Among Us).  This fungus – a yeast really – is found in a number of species of trees (primarily Douglas fir & Western hemlock) and in the soil.  It can be spread by the wind, particularly during the warmer summer months.


This fungus has a wide host range, having been found to infect humans, cats, dogs, sheep, ferrets, llamas, elk, alpacas, and even porpoises (Cite).


Unlike its better known cousin C. neoformans which generally infects people with weakened immune system – C. gattii often infects those with healthy immune systems.  And unlike its behavior in the South Pacific (primarily Australia & New Guinea) – where it was usually seen causing neurological infections – this new cold-adapted strain tends to cause more pulmonary infections.


This from the open access journal mBio.


Cryptococcus gattii in North American Pacific Northwest: Whole-Population Genome Analysis Provides Insights into Species Evolution and Dispersal

David M. Engelthalera, Nathan D. Hicksa, John D. Gillecea, Chandler C. Roea, James M. Schuppa, Elizabeth M. Driebea, Felix Gilgadob, Fabian Carricondeb,c, Luciana Trillesb,d, Carolina Firacativeb,e, Popchai Ngamskulrungrojb,f, Elizabeth Castañedae, Marcia dos Santos Lazerad, Marcia S. C. Melhemg, Åsa Pérez-Bercoffb,h, Gavin Huttleyh, Tania C. Sorrellb, Kerstin Voelzi,j, Robin C. Mayi,j, Matthew C. Fisherk, George R. Thompson IIIl, Shawn R. Lockhartm, Paul Keima,n, Wieland Meyerb


The emergence of distinct populations of Cryptococcus gattii in the temperate North American Pacific Northwest (PNW) was surprising, as this species was previously thought to be confined to tropical and semitropical regions. Beyond a new habitat niche, the dominant emergent population displayed increased virulence and caused primary pulmonary disease, as opposed to the predominantly neurologic disease seen previously elsewhere.

Whole-genome sequencing was performed on 118 C. gattii isolates, including the PNW subtypes and the global diversity of molecular type VGII, to better ascertain the natural source and genomic adaptations leading to the emergence of infection in the PNW. Overall, the VGII population was highly diverse, demonstrating large numbers of mutational and recombinational events; however, the three dominant subtypes from the PNW were of low diversity and were completely clonal. Although strains of VGII were found on at least five continents, all genetic subpopulations were represented or were most closely related to strains from South America.

The phylogenetic data are consistent with multiple dispersal events from South America to North America and elsewhere. Numerous gene content differences were identified between the emergent clones and other VGII lineages, including genes potentially related to habitat adaptation, virulence, and pathology.

Evidence was also found for possible gene introgression from Cryptococcus neoformans var. grubii that is rarely seen in global C. gattii but that was present in all PNW populations. These findings provide greater understanding of C. gattii evolution in North America and support extensive evolution in, and dispersal from, South America.

The good news is that C. gattii infections in the United States remain exceedingly rare, and most people who are exposed (which undoubtedly are millions of people every year) develop no illness or symptoms. 

This from the CDC’s C. gattii cryptococcosis webpage:

C. gattii cryptococcosis Statistics

C. gattii cryptococcosis is considered to be an emerging infection in the United States and is very rare. Approximately 100 infections were documented in the U.S. between 2004 and 2011, almost all of which came from Oregon and Washington.

C. gattii infections are under public health surveillance, and have been reportable in Oregon and Washington since autumn of 2011. This means that healthcare providers and laboratories in these states are required to collect certain information on each case, and report this information to the appropriate local or state public health authority.


The bad news, is there is really not much you can do to prevent infection:

How can I prevent infection with Cryptococcus gattii?

There are no formal recommendations for preventing C. gattii infection. Most people breathe in small amounts of many different types of fungal spores every day but never become sick. However, if you have symptoms that you think may be caused by C. gattii, you should see a doctor.


The authors write:


We provide evidence that the PNW strains originated from South America and identified numerous genes potentially related to habitat adaptation, virulence expression, and clinical presentation. Characterization of these genetic features may lead to improved diagnostics and therapies for such fungal infections. The data indicate that there were multiple recent introductions of C. gattii into the PNW. Public health vigilance is warranted for emergence in regions where C. gattii is not thought to be endemic.

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