Spatial and temporal sequence of capsule construction in <i>Cryptococcus neoformans</i>

Pierini, Lynda M.; Doering, Tamara L.

doi:10.1046/j.1365-2958.2001.02504.x

Cited by 80 publications

(100 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The highly entangled fibers of isolated GXM, visible by STEM, formed supra-structures reminiscent of the polysaccharide network observed in the capsule by freeze-fracture electron microscopy of whole cells (52,53). This suggests that GXM in the capsule and exopolysaccharide preparations are similar.…”

Section: Discussionmentioning

confidence: 72%

The Physical Properties of the Capsular Polysaccharides from Cryptococcus neoformans Suggest Features for Capsule Construction

McFadden¹,

Jesus

Casadevall

2006

Journal of Biological Chemistry

127

161

View full text Add to dashboard Cite

The most distinctive feature of the human pathogenic fungus is a polysaccharide capsule that is essential for virulence and is composed primarily of glucuronoxylomannan (GXM) and galactoxylomannan (GalXM). GXM mediates multiple deleterious effects on host immune function, yet relatively little is known about its physical properties. The average mass of Cryptococcus neoformans GXM from four antigenically different strains ranged from 1.7 to 7 ؋ 10 6 daltons as calculated from Zimm plots of light-scattering data. GalXM was significantly smaller than GXM, with an average mass of 1 ؋ 10 5 daltons. These molecular masses imply that GalXM is the most numerous polysaccharide in the capsule on a molar basis. The radius of gyration of the capsular polysaccharides ranged between 68 and 208 nm. Viscosity measurements suggest that neither polysaccharide altered fluid dynamics during infection since GXM behaved in solution as a polyelectrolyte and GalXM did not increase solution viscosity. Immunoblot analysis indicated heterogeneity within GXM. In agreement with this, scanning transmission electron microscopy of GXM preparations revealed a tangled network of two different types of molecules. Mass per length measurements from light scattering and scanning transmission electron microscopy were consistent and suggested GXM molecules self-associate. A mechanism for capsule growth is proposed based on the extracellular release and entanglement of GXM molecules.

show abstract

Section: Discussionmentioning

confidence: 72%

The Physical Properties of the Capsular Polysaccharides from Cryptococcus neoformans Suggest Features for Capsule Construction

McFadden¹,

Jesus

Casadevall

2006

Journal of Biological Chemistry

127

161

View full text Add to dashboard Cite

show abstract

“…Furthermore, the significant increase in yeast sizes, as well as the visualization of big granules of CRND-8-positive material, inside yeast cells that were surrounded by an inner ring of E1-specific structures and an outer ring of CRND-8-specific structures as soon as 6 hours after inoculation suggested synthesis of new material (and not degradation of the original material even though both events could coexist). Thus, our results suggest that C. neoformans may synthesize polysaccharides in vivo to create a new capsule structure by shedding new material from the cell and deposition/association with distal part of the old structure or by new material interspaced with old material, according to two schemes that were discarded by Pierini and Doering 31 in their in vitro demonstration. In addition to raising the question of how the capsule is synthesized in vivo during infection, our results showed that invasion of organs and dissemination were associated with dynamic changes that differ depending on the organ infected.…”

Section: Discussionmentioning

confidence: 84%

Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier

Charlier

Chrétien

Baudrimont

et al. 2005

The American Journal of Pathology

187

188

View full text Add to dashboard Cite

Cryptococcus neoformans is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.

show abstract

“…The capsular polysaccharide of C. neoformans is thinner over budding cells (Cassone et al, 1974) and qualitatively different from the parental polysaccharide (Feldmesser et al, 2000). In fact, the capsule of buds results from new synthesis rather than from parasitism of capsule present on the parent cell (Pierini & Doering, 2001). The findings of de novo synthesis of melanin and capsule by buds of C. neoformans is consistent with prior data demonstrating localized synthesis of other cell wall constituents in buds of Candida albicans (Osumi, 1998) and S. cerevisiae (Cid et al, 2002;Drees et al, 2001;Sekiya-Kawasaki et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Budding of melanized Cryptococcus neoformans in the presence or absence of l-dopa

Nosanchuk

Casadevall

2003

Microbiology

View full text Add to dashboard Cite

Cryptococcus neoformans is a pathogenic fungus that produces melanin when incubated in the presence of certain phenolic substrates such as L-3,4-dihydroxyphenylalanine (L-dopa). Melanin is an enigmatic polymer that is deposited in the cell wall and contributes to virulence. Substantial progress has been made in understanding the synthesis of melanin and the mechanisms by which it contributes to virulence, but relatively little is known about how melanin is rearranged during growth and budding. In this study we used transmission and scanning electron microscopy and immunofluorescence of melanized cells and melanin 'ghosts' to study the process of melanization during replication. Budding in melanized C. neoformans results in focal disruption of cell-wall melanin at the bud site. In the presence of L-dopa, bud-related melanin defects are repaired and daughter cells are melanized. However, in the absence of substrate, mother cells cannot repair their melanin defects and daughter cells are non-melanized. Hence, melanin in the parent cell is not carried to the daughter cells, but rather is synthesized de novo in buds. These results imply that melanin remodelling occurs during cell growth in a process that involves degradation and synthesis at sites of budding. INTRODUCTIONCryptococcus neoformans is an encapsulated, environmental fungus that can cause life-threatening meningitis, particularly in immunocompromised individuals. The ability of C. neoformans to make melanin was discovered in the early 1960s (Staib, 1962(Staib, , 1963 and was associated with virulence in the 1980s Rhodes et al., 1982). Melanins are rigid, acid-resistant polymers of uncertain structure that are found in all biological kingdoms (Hill, 1992). The synthesis of melanin by C. neoformans occurs only in the presence of phenolic compounds, such as L-3,4-dihydroxyphenylalanine (L-dopa), and is catalysed by a laccase Williamson, 1994). The C. neoformans laccase has recently been shown to be tightly associated with the cell wall by a hydrolysable bond (Zhu et al., 2001). When the fungus grows in the presence of phenolic compounds, melanin is deposited in the cell wall (Wang et al., 1995) and comprises approximately 15 % of the dry weight of late-stationary-phase melanized C. neoformans (Wang & Casadevall, 1996). C. neoformans is melanized in the environment (Nosanchuk et al., 1999b) and during human infection (Nosanchuk et al., 2000). In the environment melanin is thought to protect the fungus against extremes of temperature (Rosas & Casadevall, 1997), ultraviolet light (Wang & Casadevall, 1994a), heavy metals (Garcia-Rivera & Casadevall, 2001) and amoeboid predators (Steenbergen et al., 2001). During infection melanin appears to function in virulence by protecting fungal cells against microbicidal oxidants (Wang & Casadevall, 1994b) and peptides (Doering et al., 1999) produced by immune effector cells. Furthermore, melanin may interfere with the development of effective cellmediated responses (Huffnagle et al., 1995) and could affect the activation ...

show abstract

Spatial and temporal sequence of capsule construction in Cryptococcus neoformans

Cited by 80 publications

References 46 publications

The Physical Properties of the Capsular Polysaccharides from Cryptococcus neoformans Suggest Features for Capsule Construction

The Physical Properties of the Capsular Polysaccharides from Cryptococcus neoformans Suggest Features for Capsule Construction

Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier

Budding of melanized Cryptococcus neoformans in the presence or absence of l-dopa

Contact Info

Product

Resources

About