Abstract
Invasive fungal infections, including cryptococcosis, are a growing threat to immunocompromised patients. Although Cryptococcus neoformans and Cryptococcus gattii are the main agents of human cryptococcosis, opportunistic infections by environmental species, such as C. liquefaciens, have been observed recently. The main Cryptococcus virulence factor is the production and secretion of polysaccharides (PS). Previously, we showed that both species produce PS of similar composition. Here, we examined the ultrastructure and biological activity of capsular and secreted PS from C. liquefaciens, and yeast pathogenicity to an invertebrate host, in comparison with C. neoformans. Ultrastructural analysis by high-resolution microscopy showed that both species produce large and complex capsules. PS from both species had indistinguishable effects on phagocytosis levels, NO production and the secretion of a variety of immune mediators. Challenge with C. liquefaciens or C. neoformans led to complete lethality of G. mellonella larvae. Treatment with C. liquefaciens PS could not protect mice against infection with C. neoformans. We conclude that polysaccharides of the environmental yeast C. liquefaciens have strikingly similar ultrastructural and biological properties to those of C. neoformans, highlighting the importance of monitoring the emergence of new fungal pathogens for which thermotolerance may be an important transitional step towards pathogenesis in humans.
Highlights
The most important and best characterized virulence factor of C. neoformans is the ability to produce polysaccharides (PS), which form an external capsule anchored to the cell surface, and are secreted[8,9,10]
C. liquefaciens, yeasts from these species were cultured under the same growth conditions and analyzed by light microscopy, and by advanced scanning electron microscopy techniques – namely high-resolution scanning electron microscopy (HRSEM) and helium ion microscopy (HIM)
We previously demonstrated that the polysaccharide capsules of C. neoformans and C. liquefaciens have similar chemical composition and different physical characteristics, C. liquefaciens pathogenicity to humans was not previously considered since the fungus is not normally able to grow at the temperatures encountered in the human host[35]
Summary
The most important and best characterized virulence factor of C. neoformans is the ability to produce polysaccharides (PS), which form an external capsule anchored to the cell surface, and are secreted[8,9,10]. Aspects of the host immune response (including antibody production, leukocyte migration, complement activity and antigen presentation) and protecting yeast cells against reactive oxygen species[10,13,14,15,16,17,18]. Extensive analysis by a variety of physico-chemical methods and optical tweezers, combined with the use of advanced electron microscopy techniques, provided key insights into capsular PS ultrastructure and other properties[23]. These data show that cryptococcal capsular and secreted PS are formed of molecules with different physico-chemical and ultrastructural properties, and that PS molecules are highly complex and branched polymeric structures whose orientation varies in different regions of the capsule[22]. Cordero and co-workers (2011) provided strong evidence that the degree of PS branching and conformation affects the biological activity of the C. neoformans capsular PS21
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