<i>Cryptococcus neoformans</i>and<i>Cryptococcus gattii</i>genes preferentially expressed during rat macrophage infection

Goulart, Letícia Silveira; Kmetzsch, Lívia; Chiapello, Laura S.; Silveira, Carolina Pereira; Crestani, Juliana; Masih, Diana T.; Vainstein, Marilene Henning

doi:10.3109/13693781003677494

Cited by 20 publications

(14 citation statements)

References 54 publications

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“…Overall, the internalized fungal cells appear to experience a nutrient-limited and stressful environment. Similar but more limited results were obtained in a study to characterize and compare the expression of C. neoformans and C. gattii genes during intracellular growth in rat peritoneal macrophages by representational difference analysis (RDA) (45).…”

supporting

confidence: 54%

Adaptation of Cryptococcus neoformans to Mammalian Hosts: Integrated Regulation of Metabolism and Virulence

et al. 2012

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The basidiomycete fungus Cryptococcus neoformans infects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system. Recent studies provide insights into mechanisms of adaptation during this transition that include the expression of antiphagocytic functions, the remodeling of central carbon metabolism, the expression of specific nutrient acquisition systems, and the response to hypoxia. Specific transcription factors regulate these functions as well as the expression of one or more of the major known virulence factors of C. neoformans. Therefore, virulence factor expression is to a large extent embedded in the regulation of a variety of functions needed for growth in mammalian hosts. In this regard, the complex integration of these processes is reminiscent of the master regulators of virulence in bacterial pathogens.

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confidence: 54%

Adaptation of Cryptococcus neoformans to Mammalian Hosts: Integrated Regulation of Metabolism and Virulence

et al. 2012

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“…Variations in myo-inositol transporters in the VGI isolates are also noteworthy because myo-inositol transport has been implicated in mating and virulence (70). Additionally, transcriptome studies revealed that the transcript for myo-inositol phosphate synthase ( MYO1 ) is abundant in vivo and that an inositol/phosphatidyl inositol phosphatase is upregulated upon phagocytosis of C. gattii by rat peritoneal macrophages (71–73). Recently, it was demonstrated that phosphatidylinositol 4-kinase is required for survival ex vivo in the hostile cerebrospinal fluid environment and within macrophages and for full virulence (74).…”

Section: Resultsmentioning

confidence: 99%

Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts

D’Souza

Kronstad

Taylor

et al. 2011

mBio

181

192

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Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance.IMPORTANCE Isolates of Cryptococcus gattii are currently causing an outbreak of cryptococcosis in western North America, and most of the cases occurred in the absence of coinfection with HIV. This pattern is therefore in stark contrast to the current global burden of one million annual cases of cryptococcosis, caused by the related species Cryptococcus neoformans, in the HIV/AIDS population. The genome sequences of two outbreak-associated major genotypes of C. gattii reported here provide insights into genome variation within and between cryptococcal species. These sequences also provide a resource to further evaluate the epidemiology of cryptococcal disease and to evaluate the role of pathogen genes in the differential interactions of C. gattii and C. neoformans with immunocompromised and immunocompetent hosts.

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“…CnAfr1 seems to interfere with the pathway of phagolysosome maturation, as the early endosome marker Rab5 and late marker Rab7 are less detected upon the overexpression of the CnAFR1 gene [ 149 ]. Moreover, Goulart and colleagues have reported the upregulation of other ABC transporters in C. neoformans cells phagocyted by peritoneal macrophages [ 150 ], highlighting the importance these transporters within the study of the Cryptococcus species survival in the host.…”

Section: Mdr Transporters In Fungal Pathogens: Playing a Role In Vmentioning

confidence: 99%

Host-Pathogen Interactions Mediated by MDR Transporters in Fungi: As Pleiotropic as it Gets!

Cavalheiro

Pais

Galocha

et al. 2018

Genes

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Fungal infections caused by Candida, Aspergillus, and Cryptococcus species are an increasing problem worldwide, associated with very high mortality rates. The successful prevalence of these human pathogens is due to their ability to thrive in stressful host niche colonization sites, to tolerate host immune system-induced stress, and to resist antifungal drugs. This review focuses on the key role played by multidrug resistance (MDR) transporters, belonging to the ATP-binding cassette (ABC), and the major facilitator superfamilies (MFS), in mediating fungal resistance to pathogenesis-related stresses. These clearly include the extrusion of antifungal drugs, with C. albicans CDR1 and MDR1 genes, and corresponding homologs in other fungal pathogens, playing a key role in this phenomenon. More recently, however, clues on the transcriptional regulation and physiological roles of MDR transporters, including the transport of lipids, ions, and small metabolites, have emerged, linking these transporters to important pathogenesis features, such as resistance to host niche environments, biofilm formation, immune system evasion, and virulence. The wider view of the activity of MDR transporters provided in this review highlights their relevance beyond drug resistance and the need to develop therapeutic strategies that successfully face the challenges posed by the pleiotropic nature of these transporters.

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Cryptococcus neoformansandCryptococcus gattiigenes preferentially expressed during rat macrophage infection

Cited by 20 publications

References 54 publications

Adaptation of Cryptococcus neoformans to Mammalian Hosts: Integrated Regulation of Metabolism and Virulence

Adaptation of Cryptococcus neoformans to Mammalian Hosts: Integrated Regulation of Metabolism and Virulence

Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts

Host-Pathogen Interactions Mediated by MDR Transporters in Fungi: As Pleiotropic as it Gets!

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