<i>Cryptococcus neoformans</i>: historical curiosity to modern pathogen

Srikanta, Deepa; Santiago-Tirado, Felipe H.; Doering, Tamara L.

doi:10.1002/yea.2997

Cited by 134 publications

(110 citation statements)

References 184 publications

(213 reference statements)

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“…Between all species, Cryptococcus neoformans and Cryptococcus gatti species complexes are the main human pathogens . Both are transmitted by inhalation and once in the alveoli, they may cause lung infections of variable extent and dissemination to other sites, especially to the CNS, via the bloodstream …”

Section: Introductionmentioning

confidence: 99%

Geographic distribution of patients affected by Cryptococcus neoformans/Cryptococcus gattii species complexes meningitis, pigeon and tree populations in Southern Brazil

Tensini

Muro

Queiroz‐Telles

et al. 2016

Mycoses

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Cryptococcal meningitis is mainly caused by members of the C. neoformans/C. gattii species complexes. The ecological niches of Cryptococcus species have extensively been studied, but its epidemiological relationship with meningitis cases is still unknown. In this study, we estimate the relationship between cryptococcal meningitis cases and tree and pigeon populations, the classical niches of members of C. neoformans/C. gattii sensu lato. We analysed the records of every patient whose cerebrospinal fluid culture yielded Cryptococcus spp. during the last 30 years at Clinical Hospital of Curitiba. Data about Curitiba's pigeon and tree distribution were obtained from Curitiba's Secretaries of Zoonosis and Environment archives. We used ArcGis9 software to plot the distribution of the pigeon and tree populations in this city as well as cryptococcal meningitis cases, distinguishing them according to the causal agent in C. neoformans or C. gattii s.l. In total, 489 cryptococcal cultures were documented, with 140 corresponding to patients eligible for this study (134 affected by C. neoformans s.l. and 6 by C. gattii s.l.). The map showed a relationship between C. neoformans s.l. patients and pigeon population. C. gattii s.l. patients were associated with neither tree nor pigeon populations, but lived close to large unbuilt, unforested areas.

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Section: Introductionmentioning

confidence: 99%

Geographic distribution of patients affected by Cryptococcus neoformans/Cryptococcus gattii species complexes meningitis, pigeon and tree populations in Southern Brazil

Tensini

Muro

Queiroz‐Telles

et al. 2016

Mycoses

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“…It is also an opportunistic pathogen that is responsible for more than 600,000 deaths per year worldwide (Park et al 2009). Multiple factors influence cryptococcal virulence (Srikanta et al 2014), including the production of protective structures like melanin and its major virulence factor, a polysaccharide capsule. Capsule polysaccharides are both displayed on the cell surface and shed from the cell.…”

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confidence: 99%

Model-driven mapping of transcriptional networks reveals the circuitry and dynamics of virulence regulation

et al. 2015

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Key steps in understanding a biological process include identifying genes that are involved and determining how they are regulated. We developed a novel method for identifying transcription factors (TFs) involved in a specific process and used it to map regulation of the key virulence factor of a deadly fungus-its capsule. The map, built from expression profiles of 41 TF mutants, includes 20 TFs not previously known to regulate virulence attributes. It also reveals a hierarchy comprising executive, midlevel, and "foreman" TFs. When grouped by temporal expression pattern, these TFs explain much of the transcriptional dynamics of capsule induction. Phenotypic analysis of TF deletion mutants revealed complex relationships among virulence factors and virulence in mice. These resources and analyses provide the first integrated, systems-level view of capsule regulation and biosynthesis. Our methods dramatically improve the efficiency with which transcriptional networks can be analyzed, making genomic approaches accessible to laboratories focused on specific physiological processes.[Supplemental material is available for this article.]In this paper we present an efficient means of comprehensively mapping the network of transcription factors (TFs) that regulate a particular physiological process. Our approach cycles through deletion of TFs, expression profiling of TF mutants, model construction, and model-directed selection of TFs for the next round of deletion. This predictive genetics approach identifies TFs that affect the process of interest, providing a valuable complement to undirected mutagenesis and screening. Simultaneously, it builds a network model that explains how the TFs affect the process, yielding novel insights into the biological system under study.Mapping the network that regulates a specific process requires knowing which TFs affect that process. One way to identify such TFs is to screen comprehensive mutant libraries, but generating such libraries is not always feasible. Furthermore, genome-scale screening assays must be fast and scalable; such assays may not exist for the process of interest or may be less sensitive than other, more laborious assays. An alternative approach is to map the targets of all TFs encoded in a genome by using methods such as chromatin-immunoprecipitation (ChIP) or large-scale TF deletion and expression analysis. However, undirected, genome-wide approaches are costly and inefficient for probing a specific biological process in detail. We report a model-guided approach that addresses all of these problems by focusing experimental effort on the TFs most likely to be involved in the process of interest. Furthermore, our approach generates a network that provides mechanistic explanations for the phenotypes of TF deletion mutants.Our approach alternates network building by using an algorithm we call NetProphet with identifying relevant TFs by using an algorithm we call PhenoProphet. NetProphet is a validated method for mapping direct, functional regulation that significantly out...

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“…Disseminated cryptococcosis, including fungal organisms found in several internal organs, which was observed in FcγRIIb−/− mice, was similar to the disseminated cryptococcosis observed in patients with compromised immune systems17. However, the lesions were limited mostly to the brain in wild-type mice, a major target organ18, as usually observed in the immuno-competent human host. Surprisingly, despite the absence of generalized lesions in wild-type mice, the brain lesions were larger than in FcγRIIb−/− mice.…”

Section: Discussionmentioning

confidence: 88%

The role of macrophages in the susceptibility of Fc gamma receptor IIb deficient mice to Cryptococcus neoformans

Surawut

Ondee

Taratummarat

et al. 2017

Sci Rep

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Dysfunctional polymorphisms of FcγRIIb, an inhibitory receptor, are associated with Systemic Lupus Erythaematosus (SLE). Cryptococcosis is an invasive fungal infection in SLE, perhaps due to the de novo immune defect. We investigated cryptococcosis in the FcγRIIb−/− mouse-lupus-model. Mortality, after intravenous C. neoformans-induced cryptococcosis, in young (8-week-old) and older (24-week-old) FcγRIIb−/− mice, was higher than in age-matched wild-types. Severe cryptococcosis in the FcγRIIb−/− mice was demonstrated by high fungal burdens in the internal organs with histological cryptococcoma-like lesions and high levels of TNF-α and IL-6, but not IL-10. Interestingly, FcγRIIb−/− macrophages demonstrated more prominent phagocytosis but did not differ in killing activity in vitro and the striking TNF-α, IL-6 and IL-10 levels, compared to wild-type cells. Indeed, in vivo macrophage depletion with liposomal clodronate attenuated the fungal burdens in FcγRIIb−/− mice, but not wild-type mice. When administered to wild-type mice, FcγRIIb−/− macrophages with phagocytosed Cryptococcus resulted in higher fungal burdens than FcγRIIb+/+ macrophages with phagocytosed Cryptococcus. These results support, at least in part, a model whereby, in FcγRIIb−/− mice, enhanced C. neoformans transmigration occurs through infected macrophages. In summary, prominent phagocytosis, with limited effective killing activity, and high pro-inflammatory cytokine production by FcγRIIb−/− macrophages were correlated with more severe cryptococcosis in FcγRIIb−/− mice.

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Cryptococcus neoformans: historical curiosity to modern pathogen

Cited by 134 publications

References 184 publications

Geographic distribution of patients affected by Cryptococcus neoformans/Cryptococcus gattii species complexes meningitis, pigeon and tree populations in Southern Brazil

Geographic distribution of patients affected by Cryptococcus neoformans/Cryptococcus gattii species complexes meningitis, pigeon and tree populations in Southern Brazil

Model-driven mapping of transcriptional networks reveals the circuitry and dynamics of virulence regulation

The role of macrophages in the susceptibility of Fc gamma receptor IIb deficient mice to Cryptococcus neoformans

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