Cryptococcosis: a model for the understanding of infectious diseases

Perfect, John R.

doi:10.1172/jci75241

Cited by 24 publications

(21 citation statements)

References 21 publications

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“…The acquisition of iron and zinc is very important for the growth of A. fumigatus. As a result, genes encoding proteins involved in the acquisition of these metal ions are essential to cause disease [122,123].…”

Section: Aspergillosismentioning

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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Section: Aspergillosismentioning

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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“…Other, relatively rare portals of entry may be the gastrointestinal tract and direct tissue inoculation via trauma [3,8]. Once inside the host, the yeast either causes acute disease or goes into latency-the specific path likely being determined by both pathogen-related factors (such as inoculum burden and phenotypic traits of the infecting strain, including virulence) and host-related factors (primarily host immune status and genetic background) [3,9]. Clinical manifestations of cryptococcal disease (or "cryptococcosis") in a susceptible host primarily involve the lungs (pneumonia, cryptococcal granuloma in lungs) and the central nervous system or CNS (meningitis or meningoencephalitis; cryptococcoma of the spine) and, less commonly, virtually every organ of the human body-especially in the immunocompromised patients [3,4,8].…”

Section: Cryptococcal Diseasementioning

confidence: 99%

Host Defense Against Cryptococcal Disease: Is There a Role for B Cells and Antibody-Mediated Immunity?

Datta

Subramaniam

2014

Curr Fungal Infect Rep

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The role of B cells and antibody-mediated immunity (AMI) is poorly understood regarding infections with the encapsulated yeast species, Cryptococcus. Human cryptococcal disease, or cryptococcosis, generally occurs in the setting of immune suppression, including deficits of T cells and other components of cell-mediated immunity (CMI), as observed in HIV/AIDS, cancer, solid-organ transplant, and similar conditions. The protective role of CMI is, therefore, well-described in the literature. However, CMI deficiencies alone cannot adequately explain the quantum of cryptococcal disease noted in human and animal populations, and a wealth of clinical and experimental data, mostly spanning the past several decades, has shed light upon a significant role of AMI in anticryptococcal immunity. Recent evidence suggests that rather than functioning discretely, these two host immune compartments work synergistically, with the AMI modulating CMI functions in order to provide a critical balance for host benefit. We describe what is currently known.

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“…One of the key fungi often encountered in this context is Cryptococcus neoformans, a basidiomycete yeast responsible for cryptococcosis and a major cause of AIDS-related mortality (11). Most commonly found associated with purine-rich bird guano, spores or desiccated yeast cells from this environmental niche are inhaled into the lungs where, in an immunocompromised individual, the fungus can disseminate to the purine-poor central nervous system to cause meningoencephalitis.…”

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confidence: 99%

GMP Synthase Is Required for Virulence Factor Production and Infection by Cryptococcus neoformans

Chitty

Tatzenko

Williams

et al. 2017

Journal of Biological Chemistry

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Edited by John M. DenuOver the last four decades the HIV pandemic and advances in medical treatments that also cause immunosuppression have produced an ever-growing cohort of individuals susceptible to opportunistic pathogens. Of these, AIDS patients are particularly vulnerable to infection by the encapsulated yeast Cryptococcus neoformans. Most commonly found in the environment in purine-rich bird guano, C. neoformans experiences a drastic change in nutrient availability during host infection, ultimately disseminating to colonize the purine-poor central nervous system. Investigating the consequences of this challenge, we have characterized C. neoformans GMP synthase, the second enzyme in the guanylate branch of de novo purine biosynthesis. We show that in the absence of GMP synthase, C. neoformans becomes a guanine auxotroph, the production of key virulence factors is compromised, and the ability to infect nematodes and mice is abolished. Activity assays performed using recombinant protein unveiled differences in substrate binding between the C. neoformans and human enzymes, with structural insights into these kinetic differences acquired via homology modeling. Collectively, these data highlight the potential of GMP synthase to be exploited in the development of new therapeutic agents for the treatment of disseminated, life-threatening fungal infections.In the past four decades there has been a dramatic escalation in the number of immunocompromised individuals (1). Although many of these are due to advances in immunosuppressive and chemotherapeutic technologies, the largest cohort is a direct result of the AIDS pandemic. Foreshadowed in 1981 with the occurrence of opportunistic Pneumocystis or human herpesvirus 8 infections in previously healthy individuals in Los Angeles (2, 3), AIDS and the lentivirus causing the disease soon gained broad public awareness (4 -6). With the advent of commercial blood testing, national blood bank screening programs were commenced in an effort to slow the spread of this emerging pandemic (7), and in 1987 the first treatment, zidovudine, marked what was thought to be an end to the crisis (8, 9). It was not, as was hoped, a miracle drug; the spread of AIDS continued across the globe and is now believed to have infected over 70 million people and killed 55 million to date (10).Since the discovery of the very first patients identified with Pneumocystis pneumonia, opportunistic fungal pathogens have been tightly linked with the AIDS pandemic. One of the key fungi often encountered in this context is Cryptococcus neoformans, a basidiomycete yeast responsible for cryptococcosis and a major cause of AIDS-related mortality (11). Most commonly found associated with purine-rich bird guano, spores or desiccated yeast cells from this environmental niche are inhaled into the lungs where, in an immunocompromised individual, the fungus can disseminate to the purine-poor central nervous system to cause meningoencephalitis.The fundamental treatment for cryptococcosis has not changed significantly ...

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Cryptococcosis: a model for the understanding of infectious diseases

Cited by 24 publications

References 21 publications

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

Update on Fungal Disease: From Establish Infection to Clinical Manifestation

Host Defense Against Cryptococcal Disease: Is There a Role for B Cells and Antibody-Mediated Immunity?

GMP Synthase Is Required for Virulence Factor Production and Infection by Cryptococcus neoformans

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