The Trehalose Synthesis Pathway Is an Integral Part of the Virulence Composite for
            <i>Cryptococcus gattii</i>

Ngamskulrungroj, Popchai; Himmelreich, Uwe; Breger, Julia; Wilson, Christabel F.; Chayakulkeeree, Methee; Krockenberger, M. B.; Malík, Richard; Daniel, Heide-Marie; Toffaletti, Dena L.; Djordjevic, Julianne T.; Mylonakis, Eleftherios; Meyer, Wieland; Perfect, John R.

doi:10.1128/iai.00565-09

Cited by 91 publications

(97 citation statements)

References 56 publications

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“…The second perspective relies on the urgent need for new antifungal therapies. The trehalose synthase pathway is widespread in the fungal kingdom where it can be part of the virulence system (23,(67)(68)(69), thus making Tps1 a potential antimicrobial target for weakening mammalian and plant pathogenic microorganisms.…”

Section: Discussionmentioning

confidence: 99%

Yeast Tolerance to Various Stresses Relies on the Trehalose-6P Synthase (Tps1) Protein, Not on Trehalose

Petitjean

Teste

François

et al. 2015

Journal of Biological Chemistry

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Background: Decades of observations strengthened the idea that trehalose is a chemical chaperone. Results: A catalytically inactive variant of the trehalose-6P synthase (Tps1) maintains cell survival and energy homeostasis under stress exposure. Conclusion: The Tps1 protein itself, not trehalose, is crucial for cell integrity. Significance: This work provides unbiased evidence for an alternative function of Tps1, a new "moonlighting" protein.

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Section: Discussionmentioning

confidence: 99%

Yeast Tolerance to Various Stresses Relies on the Trehalose-6P Synthase (Tps1) Protein, Not on Trehalose

Petitjean

Teste

François

et al. 2015

Journal of Biological Chemistry

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“…Mechanistically, Wilson and colleagues showed in Magnaporthe that control of nitrogen metabolism and pathogenicity was integrated with trehalose metabolism; Tps1 is required for proper regulation of the nitrogen repressor NMR1 (12). The latter finding is intriguing, as recent data regarding the NMR1 homolog TAR1 in C. neoformans demonstrate the relationship of nitrogen regulation to melanin production, which is a major virulence factor for C. neoformans (13), and the trehalose pathway has signal control on the cryptococcal virulence composite (14,15).…”

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confidence: 92%

Nitrogen Source-Dependent Capsule Induction in Human-Pathogenic Cryptococcus Species

et al. 2013

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Cryptococcus neoformans and C. gattii cause meningoencephalitis and are an increasing human health threat. These pathogenic Cryptococcus species are neurotropic and persist in the cerebrospinal fluid (CSF) of the mammalian host during infection. In order to survive in the host, pathogenic fungi must procure nutrients, such as carbon and nitrogen, from the CSF. To enhance our understanding of nutrient acquisition during central nervous system infection by Cryptococcus species, we examined the utilization of nitrogen sources available in CSF. We screened for the growth and capsule production of 817 global environmental and clinical isolates on various sources of nitrogen. Both environmental and clinical strains grew robustly on uric acid, Casamino Acids, creatinine, and asparagine as sole nitrogen sources. Urea induced the greatest magnitude of capsule induction. This induction was greater in Cryptococcus gattii than in C. neoformans. We confirmed the ability of nonpreferred nitrogen sources to increase capsule production in pathogenic species of Cryptococcus. Since urea is metabolized to ammonia and CO 2 (a known signal for capsule induction), we examined urea metabolism mutants for their transcriptional response to urea regarding capsule production. The transcriptional profile of C. neoformans under urea-supplemented conditions revealed both similar and unique responses to other capsule-inducing conditions, including both intra-and extracellular urea utilization. As one of the most abundant nitrogen sources in the CSF, the ability of Cryptococcus to import urea and induce capsule production may substantially aid this yeast's survival and propagation in the host. Cryptococcus neoformans is a pathogenic, basidiomycete yeast responsible for causing meningoencephalitis in immunocompromised individuals. Distributed worldwide, it is the fourth largest infectious disease killer in sub-Saharan Africa as a complication of the AIDS epidemic (1). Because of the mortality and increasing incidence of cryptococcosis, it is imperative that we understand all aspects of this pathogen-host interaction and the methods of C. neoformans survival in an attempt to disrupt them.As with carbon assimilation (2), nitrogen metabolism is fundamentally critical for the survival of fungal pathogens within their plant or animal hosts. For instance, Lau and Hamer reported the influence of nitrogen regulatory elements on the expression of the Magnaporthe grisea pathogenicity gene MPG1 (3). In their study, novel nitrogen regulatory elements NPR1 and NPR2 were shown to be required for expression of MPG1 and the npr1 and npr2 mutant strains were avirulent on barley. Lau and Hamer also demonstrated that the global nitrogen regulatory transcription factor NUT1, a homolog of the Neurospora crassa NIT2 and Aspergillus nidulans areA transcription factor genes, was also partly responsible for MPG1 expression under nitrogen starvation. However, the complexity of the regulation of pathogenicity through nitrogen pathways in fungi is apparent, as strains wit...

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“…Several studies have shown that C. neoformans and C. gattii, share the same key virulence factors already known [139,140], although there are reports that some virulence attributes are specific for each species [141][142][143][144]. In this context, it can be mentioned that superoxide dismutase (Sod1, a prominent antioxidant) is required for virulence of C. gattii, but not for C. neoformans [145].…”

Section: Cryptococcosismentioning

confidence: 99%

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

Melo¹,

Scorzoni²,

Rossi³

et al. 2017

J Biotechnol Biomater

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Fungal diseases have emerged as an important cause of morbidity and mortality, especially among immunocompromised patients. Pathogenic fungi have evolved an array of virulence factors to survive within the host and to outwit immune defenses. Fungi may cause a wide range of diseases in humans that range in extent from superficial to disseminated infections. Generally, the site of infections classifies the type of fungal disease, which can be divided into superficial, cutaneous, subcutaneous and systemic. In addition, the fungal virulence factors determine whether the infection will become established in the host. A primary pathogen may infect an immunologically normal host, whereas, an opportunistic pathogen requires some compromise of the host immune defenses in order for the infection to become established. This article covers the main fungi that are responsible for the increase of the fungal infections.Keywords: Fungal infections; Virulence; Yeast; Opportunistic infections; Endemic mycosis Fungal InfectionsFungal diseases have changed constantly in the last years. The virulence of these microorganisms has been adapted according to the human host, promoting a range of clinical manifestation. Several are the ways by which fungi promote a disease depending on human body part involved by the microorganism and the immunologic system of the host [1].In this review, we discuss the main fungal pathogens responsible for causing several diseases, highlighting on their virulence associate to clinical manifestation and the difficulty to accomplish the treatment. Superficial and cutaneous fungal diseasesSuperficial and cutaneous fungal infections are very common and occur worldwide affecting millions of people, especially immunocompromised patients. The most common types of these infections are dermatophytosis (tinea or ringworm), pityriasis versicolor (formerly tinea versicolor) and candidiasis (moniliasis). These occur by fungal invasion into the skin, keratinized tissues and mucous membranes [2]. Trichosporon and Fusarium species also cause superficial fungal infection, but also may be considered an invasive pathogen that may cause a systemic infection [3,4].Dermatophytosis: Dermatophytes are fungi that invade keratinized structures of humans and animals producing a condition called dermatophytosis or, more commonly, tinea [5,6]. These fungi belong to three main genera Trichophyton, Microsporum and Epidermophyton, of these T. rubrum is the most prevalent species worldwide [7,8]. The mechanisms of pathogenicity of these fungi are not yet well understood. There are several studies focusing on keratinolytic proteases (keratinases) produced by dermatophytes, but it is not known how these fungi regulate the use of these proteases to obtain nutrients from the stratum corneum substrate they invade, and whether there are additional roles of these proteins in adhesion and immunomodulation [9].To establish the infection, the contact of arthroconidia or hyphal fragmens with the host skin is essential. The fungi express spe...

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The Trehalose Synthesis Pathway Is an Integral Part of the Virulence Composite for Cryptococcus gattii

Cited by 91 publications

References 56 publications

Yeast Tolerance to Various Stresses Relies on the Trehalose-6P Synthase (Tps1) Protein, Not on Trehalose

Yeast Tolerance to Various Stresses Relies on the Trehalose-6P Synthase (Tps1) Protein, Not on Trehalose

Nitrogen Source-Dependent Capsule Induction in Human-Pathogenic Cryptococcus Species

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

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