Spores as Infectious Propagules ofCryptococcus neoformans

Abstract

Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic fungi that cause pneumonia and meningitis in both immunocompromised and immunocompetent hosts and are a significant global infectious disease risk. Both species are found in the environment and are acquired via inhalation, leading to an initial pulmonary infection. The infectious propagule is unknown but is hypothesized to be small desiccated yeast cells or spores produced by sexual reproduction (opposite-or same-sex mating). Here we characterize the morphology, germination properties, and virulence of spores. A comparative morphological analysis of hyphae and spores produced by opposite-sex mating, same-sex mating, and self-fertile diploid strains was conducted by scanning electron microscopy, yielding insight into hyphal/basidial morphology and spore size, structure, and surface properties. Spores isolated by microdissection were found to readily germinate even on water agarose medium. Thus, nutritional signals do not appear to be required to stimulate spore germination, and as-yet-unknown environmental factors may normally constrain germination in nature. As few as 500 CFU of a spore-enriched infectious inoculum (ϳ95% spores) of serotype A C. neoformans var. grubii were fully virulent (100% lethal infection) in both a murine inhalation virulence model and the invertebrate model host Galleria mellonella. In contrast to a previous report on C. neoformans var. neoformans, spores of C. neoformans var. grubii were not more infectious than yeast cells. Molecular analysis of isolates recovered from tissues of infected mice (lung, spleen, and brain) provides evidence for infection and dissemination by recombinant spore products. These studies provide a detailed morphological and physiological analysis of the spore and document that spores can serve as infectious propagules.

Primer aislamiento ambiental de Cryptococcus gattii de serotipo B, en Cúcuta, Colombia

“…In addition, the identification of new habitats of C. gattii is very important and it is possible that the presence of yeasts in soil is the source of contamination of immunocompetent individuals, because the yeast can be dispersed by the air and patients acquire the cryptococcal infection from environmental sources (8,15). For further studies, other environmental sources such as pigeon droppings or biodegraded wood could be included to increase the possibility of recovering more isolates.…”

“…neoformans, serotype D, have been mostly isolated from immunocompromised host with disseminated cryptococcosis, while C. gattii, serotypes B and C is most often associated with neurological disorders in hosts with normal immunity (2)(3)(4) and with disease in domestic animals (5)(6)(7). Infections are mainly acquired via inhalation of basidiospores from the environment, which are the principal infectious propagules for the C. neoformans/ C. gattii species complex (8).…”

ANaganishiain high places: functioning populations or dormant cells from the atmosphere?

“…For most pathogenic Cryptococcus species, sexual spores are only known to be produced in the laboratory and have not been found in nature or in clinical samples (Velagapudi et al 2009); however, Nielsen et al (2007) found that Cryptococcus neoformans can mate on pigeon guano. To our knowledge, no extremophilic members of the genus Naganishia are known to have a sexual stage (Barnett et al 2000), but this could just be because the source habitat (reservoir) for this group has not yet been discovered.…”

Fungal Morphogenesis

“…By definition, a basidiomycete fungus (e.g., Cryptococcus neoformans) produces hyphal structures during sexual differentiation that distinguish it from ascomycetes (Kwon-Chung 1975, 1976. Spores produced by Cryptococcus hyphae are quite infectious and may be the primary particle inhaled during a natural infection (Giles et al 2009;Velagapudi et al 2009). Therefore, the transition to hyphal growth that supports sporulation is required for the wide dissemination of Cryptococcus in the environment, as well as for infection of its mammalian hosts.…”