Posts Tagged ‘Cryptococcus’

Cryptococcus spores race the host for survival

Friday, July 9th, 2010

Cryptococcus Sporulation is a strategy used by many organisms, including bacteria, fungi, protozoa, algae, and ferns to survive conditions that are too harsh to sustain vegetative growth. Survival is generally facilitated by developing specialized cells (spores) with physical properties that confer resistance to environmental assault. Many organisms also produce spores on specialized structures that are adapted for efficient dispersal via wind or water currents. Through these adaptations, sporulation is an effective mechanism to either persist until local conditions improve or disperse to new environments conducive for growth.

For pathogenic microbes, favorable growth conditions are often found in a mammalian host, resulting in serious consequences for human health. For example, spores of protozoan parasites, such as the oocytes of Cryptosporidium sp., can be found in untreated or fecal waste-contaminated water and have been estimated to cause >50% of water-borne parasitic disease worldwide, including major outbreaks in the United States. Spores of bacterial pathogens, such as those produced by Bacillus anthracis, are extremely resistant to physical and chemical insult, making B. anthracis a potentially devastating biological weapon. In fungi, spores are thought to be the infectious particles of many fungal pathogens. This has been shown rigorously for a number of plant fungal pathogens, such as the wheat rusts, Puccinia sp., which disperse globally on an annual basis and cause damage to food crops totaling 3 billion dollars per year.

Among human fungal pathogens, spores are presumed infectious particles for many organisms. The infection-causing potential of spores from human fungal pathogens is exemplified by Coccidioides immitis, as few as 10 spores can establish disease and cause fatal disease. Because these highly infectious spores are adapted for wind dispersal, C. immitis spores, similar to spores from B. anthracis, have been postulated to be serious threats as biological weapons. Despite the demonstrated capacity of spores from human fungal pathogens to infect mammalian hosts, the specific roles that spores play in establishing disease are less clear.

Dueling in the lung: how Cryptococcus spores race the host for survival. Curr Opin Microbiol. Jun 4 2010
Many human fungal pathogens infect people when they are inhaled as spores. Despite the serious impact of fungal spores on human health, little is known about their basic properties or how they interact with the host. This is particularly true for Cryptococcus neoformans, a human fungal pathogen that causes more than 600,000 deaths annually. Spores of C. neoformans have not been well characterized previously because of technical challenges in isolating them; however, recent advances in spore isolation have lead to the first direct analyses of spores. Novel insights into the spore-host interaction, specifically how spores interact with alveolar macrophages, have provided a new model of cryptococcosis that could have broad implications for human fungal pathogenesis.

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New Strain of Virulent Airborne Fungus Looks Set to Spread

Friday, April 23rd, 2010

Cryptococcus Emerging and reemerging infectious diseases are increasing worldwide and represent a major public health concern. One class of emerging human and animal diseases is caused by fungi. A new study examines an outbreak of a fungal infection, Cryptococcus gattii, in the Pacific Northwest of the United States. This fungus has been considered a tropical fungus, but emerged to cause an outbreak in the temperate climes of Vancouver Island in 1999 that is now causing disease in humans and animals in the United States. Because of the way an Oregon-specific strain of the fungus is reproducing and spreading, it will likely move into California and other adjacent areas. This novel fungus is worrisome because it appears to be a threat to otherwise healthy people. Typically, we more often see this fungal disease associated with transplant recipients and HIV-infected patients, but that is not what we are seeing in this case. VGIIc, the new Oregon strain, has yielded dozens of isolates from many specimens, including domesticated animals like cats, dogs and sheep – even an unlucky alpaca. Most of those are nonmigratory animals, which suggests that the animals probably didn’t bring the pathogen from some other region but, rather, acquired it locally. Using molecular techniques, the geneticists uncovered clues that showed the Oregon-only fungal strain most likely arose recently, parallel to the outbreak of C. gattii that began in Canada in 1999 that has now spread into Washington and Oregon.

The researchers found that the novel genotype (VGIIc) is now a major source of C. gattii illness in Oregon. Because C. gattii types had previously been found in tropical areas, the authors speculate that environmental changes may be responsible for the evolution and emergence of this pathogen. Determining the exact origin of the VGIIc type is difficult, and sampling thus far has failed to turn up isolates in Oregon soil, water or trees. The mortality rate for recent C. gattii cases in the Pacific Northwest is running at approximately 25 percent, or 5 out of 21 cases analyzed in the United States, compared to a mortality rate of 8.7 percent of 218 cases in British Columbia, Canada. Most C. gattii infections follow a more complicated clinical course in people than does the more common Cryptococcus neoformans. Symptoms can appear two to several months after exposure, and while most people never develop symptoms, those infected may have a cough lasting weeks, sharp chest pain, shortness of breath, headache (related to meningitis), fever, night time sweats and weight loss. In animals the symptoms are a runny nose, breathing problems, nervous system problems and raised bumps under the skin. While C. gattii can be treated, it cannot be prevented; there is no vaccine. Because the strain is so virulent when it infects some humans and animals, the researchers are calling for greater awareness and vigilance in testing. Some strains of C. gattii are not more virulent than C. neoformans, for example, but doctors need to know what type they are dealing with.

Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States. PLoS Pathog 6(4): e1000850. doi:10.1371/journal.ppat.1000850
Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and to a lesser extent in immunocompromised hosts. The highest incidence for this disease is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions including mainland British Columbia and the United States. This outbreak is caused predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition, a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness in the region. Through molecular epidemiology and population analysis of MLST and VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently. The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination in the global VGII population. This illustrates two hallmarks of emerging outbreaks: high clonality and the emergence of novel genotypes via recombination. In macrophage and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the United States are highly virulent compared to similar non-outbreak VGIIa/major-related isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major outbreak genotype from related but distinguishable less-virulent genotypes isolated from other geographic regions. Our evidence documents emerging hypervirulent genotypes in the United States that may expand further and provides insight into the possible molecular and geographic origins of the outbreak.

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