Cas3p Belongs to a Seven-Member Family of Capsule Structure Designer Proteins

Moyrand, Frédérique; Chang, Yun C.; Himmelreich, Uwe; Kwon‐Chung, Kyung J.; Janbon, Guilhem

doi:10.1128/ec.3.6.1513-1524.2004

Cited by 54 publications

(71 citation statements)

References 55 publications

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“…An exception is the laccase gene LAC1, created in R265, the virulent VGIIa strain from the Vancouver Island outbreak, the overexpression of which was associated with increased virulence in a mouse inhalation model (137). In that same study, disruption of CAS1, which is associated with the construction of the polysaccharide capsule backbone in C. neoformans (138), did not affect capsule size but, when overexpressed, was associated with hypervirulence in mice. Disruption of the signal transduction pathway molecule MPK1, which causes defective melanin synthesis and cell wall integrity, was associated with reduced virulence (137).…”

Section: Cryptococcal Virulence Determinantsmentioning

confidence: 78%

Cryptococcus gattii Infections

2014

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SUMMARY Understanding of the taxonomy and phylogeny of Cryptococcus gattii has been advanced by modern molecular techniques. C. gattii probably diverged from Cryptococcus neoformans between 16 million and 160 million years ago, depending on the dating methods applied, and maintains diversity by recombining in nature. South America is the likely source of the virulent C. gattii VGII molecular types that have emerged in North America. C. gattii shares major virulence determinants with C. neoformans , although genomic and transcriptomic studies revealed that despite similar genomes, the VGIIa and VGIIb subtypes employ very different transcriptional circuits and manifest differences in virulence phenotypes. Preliminary evidence suggests that C. gattii VGII causes severe lung disease and death without dissemination, whereas C. neoformans disseminates readily to the central nervous system (CNS) and causes death from meningoencephalitis. Overall, currently available data indicate that the C. gattii VGI, VGII, and VGIII molecular types more commonly affect nonimmunocompromised hosts, in contrast to VGIV. New, rapid, cheap diagnostic tests and imaging modalities are assisting early diagnosis and enabling better outcomes of cerebral cryptococcosis. Complications of CNS infection include increased intracranial pressure, severe neurological sequelae, and development of immune reconstitution syndrome, although the mortality rate is low. C. gattii VGII isolates may exhibit higher fluconazole MICs than other genotypes. Optimal therapeutic regimens are yet to be determined; in most cases, initial therapy with amphotericin B and 5-flucytosine is recommended.

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Section: Cryptococcal Virulence Determinantsmentioning

confidence: 78%

Cryptococcus gattii Infections

2014

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“…It is also possible that CAP59 and CAP64 are not transcriptionally regulated, because little difference in their expression levels was found under capsule-inducing and noninducing conditions (48). On the other hand, two CAP64 homologs, CAS31 and CAS32, as well as the CAS1 and CAS2 genes, which are all involved in modifying capsule structure (40,57,58), were upregulated 2.0-to 2.8-fold (Table 3). These findings suggest that internalized C. neoformans cells may produce a capsule of different structure or composition from that of free-living cells.…”

Section: Induction Of Genes With Known Virulence Rolesmentioning

confidence: 99%

Cryptococcus neoformansGene Expression during Murine Macrophage Infection

Fan¹,

Kraus²,

Boily³

et al. 2005

Eukaryot Cell

179

177

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The fungal pathogen Cryptococcus neoformans survives phagocytosis by macrophages and proliferates within, ultimately establishing latent infection as a facultative intracellular pathogen that can escape macrophage control to cause disseminated disease. This process is hypothesized to be important for C. neoformans pathogenesis; however, it is poorly understood how C. neoformans adapts to and overcomes the hostile intracellular environment of the macrophage. Using DNA microarray technology, we have investigated the transcriptional response of C. neoformans to phagocytosis by murine macrophages. The expression profiles of several genes were verified using quantitative reverse transcription-PCR and a green fluorescent protein reporter strain. Multiple membrane transporters for hexoses, amino acids, and iron were up-regulated, as well as genes involved in responses to oxidative stress. Genes involved in autophagy, peroxisome function, and lipid metabolism were also induced. Interestingly, almost the entire mating type locus displayed increased expression 24 h after internalization, suggesting an intrinsic connection between infection and the MAT locus. Genes in the Gpa1-cyclic AMP-protein kinase A pathway were also up-regulated. Both gpa1 and pka1 mutants were found to be compromised in macrophage infection, confirming the important role of this virulence pathway. A large proportion of the repressed genes are involved in ribosome-related functions, rRNA processing, and translation initiation/elongation, implicating a reduction in translation as a central response to phagocytosis. In summary, this gene expression profile allows us to interpret the adaptation of C. neoformans to the intracellular infection process and informs the search for genes encoding novel virulence attributes.

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“…Gene disruptions were carried out as previously described (22,23). The disruption cassette was constructed by PCR fusion, using a strategy similar to that used by Kuwayama and colleagues (15).…”

Section: Methodsmentioning

confidence: 99%

Cryptococcus neoformans Senses CO ₂ through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1

et al. 2006

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Cryptococcus neoformans, a fungal pathogen of humans, causes fatal meningitis in immunocompromised patients. Its virulence is mainly determined by the elaboration of a polysaccharide capsule surrounding its cell wall. During its life, C. neoformans is confronted with and responds to dramatic variations in CO 2 concentrations; one important morphological change triggered by the shift from its natural habitat (0.033% CO 2 ) to infected hosts (5% CO 2 ) is the induction of capsule biosynthesis. In cells, CO 2 is hydrated to bicarbonate in a spontaneous reaction that is accelerated by carbonic anhydrases. Here we show that C. neoformans contains two ␤-class carbonic anhydrases, Can1 and Can2. We further demonstrate that CAN2, but not CAN1, is abundantly expressed and essential for the growth of C. neoformans in its natural environment, where CO 2 concentrations are limiting. Structural studies reveal that Can2 forms a homodimer in solution. Our data reveal Can2 to be the main carbonic anhydrase and suggest a physiological role for bicarbonate during C. neoformans growth. Bicarbonate directly activates the C. neoformans Cac1 adenylyl cyclase required for capsule synthesis. We show that this specific activation is optimal at physiological pH.

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Cas3p Belongs to a Seven-Member Family of Capsule Structure Designer Proteins

Cited by 54 publications

References 55 publications

Cryptococcus gattii Infections

Cryptococcus gattii Infections

Cryptococcus neoformansGene Expression during Murine Macrophage Infection

Cryptococcus neoformans Senses CO ₂ through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1

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Cas3p Belongs to a Seven-Member Family of Capsule Structure Designer Proteins

Cited by 54 publications

References 55 publications

Cryptococcus gattii Infections

Cryptococcus gattii Infections

Cryptococcus neoformansGene Expression during Murine Macrophage Infection

Cryptococcus neoformans Senses CO 2 through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1

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Product

Resources

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Cryptococcus neoformans Senses CO ₂ through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1