Dormancy in Cryptococcus neoformans: 60 years of accumulating evidence

Abstract

Cryptococcus neoformans is an opportunistic yeast that is present worldwide and interacts with various organisms. In humans, it is responsible for cryptococcosis, a deadly invasive fungal infection which represents around 220,000 cases per year worldwide. Starting from the natural history of the disease in humans, there is accumulating evidence on the capacity of this organism to enter dormancy. In response to the harsh host environment, the yeast is able to adapt dramatically and escape the vigilance of the host's immune cell to survive. Indeed, the yeast exposed to the host takes on pleiotropic phenotypes, enabling the generation of populations in heterogenous states, including dormancy, to eventually survive at low metabolic cost and revive in favorable conditions. The concept of dormancy has been validated in C. neoformans from both epidemiological and genotyping data, and more recently from the biological point of view with the characterization of dormancy through the description of viable but non-culturable cells.

Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018

“…Epidemiological and genetic data support transmission of C. neoformans from environmental sources including pigeon guano to humans. Infections originate by inhalation of spores directly into the lungs and can be asymptomatic, with some latent cases persisting for months or years before reactivation [8][9][10].…”

Microbe Profile: Cryptococcus neoformans species complex

“…Cryptococcus does not transmit from humans to humans. Environmental exposure is common and asymptomatic in the general population as the fungus is either cleared or becomes dormant [6]. Fatal systemic cryptococcosis, partly attributable to reactivation of dormant infections, occurs commonly in immunocompromised individuals.…”

Cryptococcal infection in haematologic malignancies and haematopoietic stem cell transplantation

“…Cryptococcus is primarily acquired via inhalation route, and its disease spectrum varies from asymptomatic colonisation to disseminated infection with central nervous system involvement. A specific feature of cryptococcosis is its latency and dormancy inside macrophages, which allows for its persistence and future ability to disseminate inside hosts 10,11 . Two different species, Cryptococcus neoformans and Cryptococcus gattii , are responsible for the vast majority of infections in humans.…”

“…A specific feature of cryptococcosis is its latency and dormancy inside macrophages, which allows for its persistence and future ability to disseminate inside hosts. 10,11 Two different species, Cryptococcus neoformans and Cryptococcus gattii, are responsible for the vast majority of infections in humans. Cryptococcus neoformans can cause disseminated infections, predominantly in pulmonary and central nervous systems (CNS), usually in immunocompromised hosts, whereas Cryptococcus gattii can affect both immunocompromised and immunocompetent, with a majority of patients developing a pneumonia and a minority developing CNS infection if immunocompromised.…”