The cause and effect of Cryptococcus interactions with the host
Section snippets
Initiation of infection by cryptococcal spores
Cryptococcus neoformans infection occurs via inhalation of desiccated yeast or spores, which germinate in the host lung (Figure 1) [1, 2, 3, 4]. Two recent studies from the Hull lab have significantly improved overall understanding of this transition [5, 6]. Barkal et al. developed a high throughput, computational method for in vitro spore germination and analysis [5]. They show that C. neoformans germination, defined as a switch from ovoid spores to round yeast, is a synchronous process
Cell cycle control in yeast phase virulence
While the importance of capsule and melanin for host evasion, immunomodulation, and stress resistance is well established, an emerging theme is the role of the cell cycle in regulating pathogenicity factor expression. The fundamental observation that, unlike model yeast, C. neoformans bud emergence can be uncoupled from DNA synthesis during host stress or nutrient limiting conditions (summarized in [11•]) has clear morphological consequences. For example, Fu et al. showed that G2 arrested cells
Host condition dependent changes in C. neoformans
The question of how pathogenicity factor expression became integrated into cell cycle control remains unexplored, however the conserved role of Usv101 in regulating cell wall synthesis genes (AGS1 (α-glucan), CHS5 (chitin), and SKO1 (β-gucan)) in C. neoformans and the distantly related, non-periodic S. cerevisiae Usv1 suggest that Usv101 is a cell wall transcription factor that has co-opted pathogenicity factor expression pathways and been incorporated into cell cycle regulation. This link may
Surviving the warm-blooded host
Thermotolerance is essential to C. neoformans virulence, and recent findings have emphasized the requirement for calcineurin-Crz1 signalling [28], the unfolded protein response [29], and amino acid permeases [30]. Capsule synthesis induction by differences in temperature varies between C. neoformans strains [31]. Analysis of the signalling networks responsible for the increased thermotolerance of the SCH9 protein kinase mutant identified the heat shock transcription factor HSF1 to have both
The immune response and interaction with cryptococci
How the different aspects of the host immune system protect against cryptococcal infection is highly complex, and our understanding of normal immunity, and the defects in immuno-compromise, are still incomplete (reviewed in [36]). A critical area of investigation is pro-inflammatory activation of macrophages. Recent clinical studies have highlighted the complexity of the immunology associated with cryptococcal meningitis in HIV positive patients (reviewed in [37]) and increased clarity on the
Initiation of cryptococcal meningitis
Cryptococcal meningitis is the life-threatening form of cryptococcosis and requires the invasion of the central nervous system (CNS) by cryptococcal yeast. Three different mechanisms for CNS invasion have been identified: first, disruption of the blood vessel endothelium integrity, second, uptake and expulsion by blood vessel cells and third, Trojan horse invasion via host macrophages. The cryptococcal matrixmetalloprotease MPR1 has been implicated in CNS invasion and adherence to endothelia in
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
ERB is supported by an Anniversary Future Leaders Fellowship from the UK Biotechnology and Biological Research Council (BB/M014525/1). SAJ is supported by a Medical Research Council and Department for International Development Career Development Award Fellowship MR/J009156 and a Krebs Institute Fellowship.
References (60)
- et al.
The roles of zinc and copper sensing in fungal pathogenesis
Curr Opin Microbiol
(2016) - et al.
Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence
Cell Host Microbe
(2013) - et al.
Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection
PLoS Pathog
(2015) - et al.
Dectin-3 is not required for protection against Cryptococcus neoformans infection
PLOS ONE
(2017) - et al.
Elucidating the pathogenesis of spores from the human fungal pathogen Cryptococcus neoformans
Infect Immun
(2009) - et al.
Cryptococcus: from environmental saprophyte to global pathogen
Nat Rev Microbiol
(2016) - et al.
A zebrafish model of cryptococcal infection reveals roles for macrophages, endothelial cells, and neutrophils in the establishment and control of sustained fungemia
Infect Immun
(2016) - et al.
Interactions of fungal pathogens with phagocytes
Nat Rev Microbiol
(2016) - et al.
Protein composition of infectious spores reveals novel sexual development and germination factors in cryptococcus
PLoS Genet
(2015) - et al.
Leveraging a high resolution microfluidic assay reveals insights into pathogenic fungal spore germination
Integr Biol (Camb)
(2016)
Genetic and environmental influences on the germination of basidiospores in the Cryptococcus neoformans species complex
Scient Rep
Sporulation: how to survive on planet Earth (and beyond)
Curr Genet
The single Cdk1-G1 cyclin of Cryptococcus neoformans is not essential for cell cycle progression, but plays important roles in the proper commitment to DNA synthesis and bud emergence in this yeast
FEMS Yeast Res
The production of monokaryotic hyphae by Cryptococcus neoformans can be induced by high temperature arrest of the cell cycle and is independent of same-sex mating
PLoS Pathog
Temporal behavior of capsule enlargement by Cryptococcus neoformans
Eukaryot Cell
Capsule growth in Cryptococcus neoformans is coordinated with cell cycle progression
MBio
Role of Cln1 during melanization of Cryptococcus neoformans
Front Microbiol
Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli
Eukaryot Cell
Investigating conservation of the cell-cycle-regulated transcriptional program in the fungal pathogen, Cryptococcus neoformans
PLoS Genet
Computational analysis reveals a key regulator of cryptococcal virulence and determinant of host response
MBio
Reciprocal functions of Cryptococcus neoformans copper homeostasis machinery during pulmonary infection and meningoencephalitis
Nature Commun
Model-driven mapping of transcriptional networks reveals the circuitry and dynamics of virulence regulation
Genome Res
Toward an integrated model of capsule regulation in Cryptococcus neoformans
PLoS Pathog
A role for LHC1 in higher order structure and complement binding of the Cryptococcus neoformans capsule
PLoS Pathog
A eukaryotic capsular polysaccharide is synthesized intracellularly and secreted via exocytosis
Mol Biol Cell
Cryptococcus neoformans UGT1 encodes a UDP-Galactose/UDP-GalNAc transporter
Glycobiology
Evasion of innate immune responses by the highly virulent cryptococcus gattii by altering capsule glucuronoxylomannan structure
Front Cell Infect Microbiol
Role of the Apt1 protein in polysaccharide secretion by Cryptococcus neoformans
Eukaryot Cell
Cryptococcus gattii capsule blocks surface recognition required for dendritic cell maturation independent of internalization and antigen processing
J Immunol
Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans
PLoS Genet
Cited by (30)
Evaluation the efficacy of some culture media in melanin production by Cryptococcus neoformans
2023, Materials Today: ProceedingsCalcium: a central player in Cryptococcus biology
2021, Fungal Biology ReviewsCitation Excerpt :Approximately 223,000 cases of cryptococcosis are reported each year globally, leading to 181,000 deaths (Rajasingham et al., 2017). The infection initiates by the inhalation of spores or desiccated yeast cells that reach the lungs, wherein immunocompetent hosts can easily eliminate these yeast cells via the immune system, or they may remain latent for a long period (Ballou and Johnston, 2017; Sabiiti and May, 2012). In immunocompromised patients, cryptococcal cells can disseminate from the lungs to the brain and frequently cause lethal meningitis if not correctly treated (Denham and Brown, 2018; Jarvis et al., 2014).
A DNA electrochemical biosensor based on homogeneous hybridization for the determination of Cryptococcus neoformans
2018, Journal of Electroanalytical ChemistryCitation Excerpt :Furthermore, in recent years, it has been paid high attention to pulmonary cryptococcosis induced by Cryptococcus neoformans. Cryptococcus neoformans can attack the lungs rapidly when patients have some immunocompromised diseases, such as organ transplant, malignant tumor and HIV infection, and then developed into acute respiratory distress syndrome (ARDS) [4–7]. At present, the common laboratory methods for identification of Cryptococcus neoformans are microbiological culture, smear and serologic antigen test.
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These authors contributed equally to this work.