Special Issue "Yeasts Are Beasts"

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (25 August 2015).

Special Issue Editor

Prof. Dr. John R. Perfect
E-Mail Website
Guest Editor
Division of Infectious Diseases & International Health, Duke University Medical Center, PO Box 3553, Durham, NC 2770, USA

Special Issue Information

Dear Colleagues,

Invasive yeast infections remain deadly complications in modern medicine. These fungi particularly attack weakened hosts and their victims; complications can range from the immune devastation of HIV infection to the circumstances of the Intensive Care Unit patient, who can suffer from a combination of foreign bodies, antibacterial exposure, and septic physiology to become a high risk host. Within the landscape of these compromised hosts, cryptococcosis and candidiasis can wreak havoc with patient health.

There have been three major outbreaks of cryptococcosis: (1) the outbreak in the late 1960’s, with the introduction of immunosuppressive agents and transplantation; (2) the outbreak during the mid-1980s through the early turn of the century, in which the outbreak followed the pandemic of HIV infections; (3) the outbreak around 2000, in Vancouver and in the Pacific North West, which was identified as a C. gattii outbreak. These three outbreaks continue. In cryptococcal infections, the principles of fungal disease pathobiology and management abound. First, mortality for cryptococcal meningoencephalitis continues to be 20-30% in resource-available environments; in resource-limited environments, mortality can reach over 50%. Clearly, our institution of optimal antifungal therapy and its delivery have substantial room for improvements. Second, cryptococcosis separates itself into three groups, including in those with underlying diseases, such as HIV or transplant recipients; the final group consists of a heterogeneous patient population with a myriad of apparent and non-apparent risks. In many respects, this latter group is the hardest to manage. Third, the lethal cryptococcal meningoencephalitis patient precisely defines the impact of immune reconstitution inflammatory syndrome (IRIS) on disease outcome. IRIS is a major clinical feature in the era of host immune modulations. Its impact on clinical disease, from increased intracranial pressure to symptomatic headaches and worsening radiographs, has become a major clinical conundrum for clinicians. Fourth, although new antifungal agents for treating cryptococcosis are not yet in the clinic, there has been an explosion of molecular pathogenesis studies on this yeast, which has allowed it to become a major fungal pathogenic model system for understanding mycologic pathobiology. Fifth, on the host side, we continue to pull back the mysteries of immune suppression, including the recent identification of anti GM-CSF antibodies as a risk factor that contributes to C. gattii infections.

Candidiasis, in all its local and invasive forms, remains the most common fungal problem to cause widespread disease in the human host.  From our antibiotic usage, with selective pressure on the microbiome, to our genetic susceptibility to neutropenia/mucositis, to the placement of a variety of catheters/foreign bodies, this relatively benign fungal colonizer can become a life-threatening infection. There are multiple species, such as C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei, which we lump under the term candidiasis, but they all have their own unique features. In the study of candidiasis, we have excellent and mature molecular tools to help understand the disease. The disease covers certain territories, such as foreign bodies and biofilms, the switching of forms from commensal to pathogen, and the development of direct drug resistance. There has now been extensive therapeutic experience with three classes of antifungal agents (polyenes, azoles, and echinocandins) in candidiasis. In fact, the echinocandins have been gaining favor as the safe and most effective class of agents for invasive candidiasis; however, with frequent use, drug resistance has again raised its ugly consequences. It is important that we develop new antifungal classes against candidiasis, but immediately, we need to strengthen our antifungal stewardships to wisely utilize our present armamentarium in prophylactic, empirical, and pre-emptive uses, and in therapy. Early diagnostic strategies and targeted treatments are essential to care for these candida superinfections, which critically modulate patient outcome.

Cryptococcosis and candidiasis are different in multiple aspects, but they critically define the immune compromised hosts today, and they represent a major stumbling block in the return to health of seriously ill patients. They are defined sentinel markers linked to the immunocompromised individual. The articles presented in this Special Issue concern various aspects of these diseases; the Special Issue will dial down into the understandings of the yeasts and the diseases they produce. It is simply important to understand the “enemy” if we want to control it.

Here is a list of topics I would suggest (including but not limited to):

Cryptococcosis

•Understanding the molecular aspect of cryptococcosis: What makes the yeast produce disease
•The outbreaks of cryptococcosis (From the rise of transplantation to the HIV pandemic and capped by the environmental resurgence in Vancouver)
•The clash of titans in cryptococcal meningitis: IRIS vs. the burden of yeasts.
•Cryptococcosis: One of the best-studied fungal diseases for treatment but what do we really know and what we need to know?

Candidiasis

•Candidiasis: From commensal to invasive disease, what does the yeast really do?
•Multiple host risk groups and how does that impact management of candidiasis.
•Foreign bodies, biofilms, antifungal susceptibility testing, and diagnostic strategies, in candidiasis: What is important and why?
•In candidiasis treatment: What are the principles and how do the treatment guidelines help or hinder management?

Prof. Dr. John R. Perfect
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


 

Keywords

  • Cryptococcal meningitis
  • Cryptococcus neoformans
  • Cryptococcus gattii
  • Immune Reconstitution Inflammatory Syndrome (IRIS)
  • Increased intracranial pressure
  • Fungal diagnostics
  • Antifungal drugs (polyenes, azoles, echinocandins)
  • Epidemiology of Invasive Fungal Diseases
  • Biofilms
  • Drug Resistance mechanisms/detection
  • Risk factor analysis
  • Prophylaxis, empirical vs pre-emptive use, and treatment
  • Outcome measurements
  • Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis ,Candida krusei

Published Papers (9 papers)

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Open AccessReview
Invasive Candidiasis in Various Patient Populations: Incorporating Non-Culture Diagnostic Tests into Rational Management Strategies
J. Fungi 2016, 2(1), 10; https://doi.org/10.3390/jof2010010 - 06 Feb 2016
Cited by 7
Abstract
Mortality rates due to invasive candidiasis remain unacceptably high, in part because the poor sensitivity and slow turn-around time of cultures delay the initiation of antifungal treatment. β-d-glucan (Fungitell) and polymerase chain reaction (PCR)-based (T2Candida) assays are FDA-approved adjuncts to cultures for diagnosing [...] Read more.
Mortality rates due to invasive candidiasis remain unacceptably high, in part because the poor sensitivity and slow turn-around time of cultures delay the initiation of antifungal treatment. β-d-glucan (Fungitell) and polymerase chain reaction (PCR)-based (T2Candida) assays are FDA-approved adjuncts to cultures for diagnosing invasive candidiasis, but their clinical roles are unclear. We propose a Bayesian framework for interpreting non-culture test results and developing rational patient management strategies, which considers test performance and types of invasive candidiasis that are most common in various patient populations. β-d-glucan sensitivity/specificity for candidemia and intra-abdominal candidiasis is ~80%/80% and ~60%/75%, respectively. In settings with 1%–10% likelihood of candidemia, anticipated β-d-glucan positive and negative predictive values are ~4%–31% and ≥97%, respectively. Corresponding values in settings with 3%–30% likelihood of intra-abdominal candidiasis are ~7%–51% and ~78%–98%. β-d-glucan is predicted to be useful in guiding antifungal treatment for wide ranges of populations at-risk for candidemia (incidence ~5%–40%) or intra-abdominal candidiasis (~7%–20%). Validated PCR-based assays should broaden windows to include populations at lower-risk for candidemia (incidence ≥~2%) and higher-risk for intra-abdominal candidiasis (up to ~40%). In the management of individual patients, non-culture tests may also have value outside of these windows. The proposals we put forth are not definitive treatment guidelines, but rather represent starting points for clinical trial design and debate by the infectious diseases community. The principles presented here will be applicable to other assays as they enter the clinic, and to existing assays as more data become available from different populations. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
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Open AccessReview
Pediatric Invasive Candidiasis: Epidemiology and Diagnosis in Children
J. Fungi 2016, 2(1), 5; https://doi.org/10.3390/jof2010005 - 08 Jan 2016
Cited by 12
Abstract
Pediatric patients present with differing underlying conditions and cytotoxic therapeutic protocols, so the differing epidemiology of invasive candidiasis in children versus adults is not surprising. Understanding the Candida species epidemiology is critical, as we often begin empiric therapy or therapy before antifungal susceptibilities [...] Read more.
Pediatric patients present with differing underlying conditions and cytotoxic therapeutic protocols, so the differing epidemiology of invasive candidiasis in children versus adults is not surprising. Understanding the Candida species epidemiology is critical, as we often begin empiric therapy or therapy before antifungal susceptibilities are known. Reports with newer molecular diagnostic assays for invasive candidiasis are rare and require more study to develop firm pediatric-specific guidance. Antifungal treatment of pediatric candidiasis is reviewed in the context of larger epidemiologic studies and the few trials completed to date. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
Open AccessReview
Colliding Epidemics and the Rise of Cryptococcosis
J. Fungi 2016, 2(1), 1; https://doi.org/10.3390/jof2010001 - 23 Dec 2015
Cited by 3
Abstract
Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in fermenting peach juice, [...] Read more.
Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in fermenting peach juice, and identified as a human pathogen in 1894 in a patient with bone lesions, this environmental pathogen has now found niches in soil, trees, birds, and domestic pets. Cryptococcosis is well recognized as an opportunistic infection and was first noted to be associated with reticuloendothelial cancers in the 1950s. Since then, advances in transplant immunology, medical science and surgical techniques have led to increasing numbers of solid organ transplantations (SOT) and hematological stem cell transplantations being performed, and the use of biological immunotherapeutics in increasingly high-risk and older individuals, have contributed to the further rise in cryptococcosis. Globally, however, the major driver for revivification of cryptococcosis is undoubtedly the HIV epidemic, particularly in Sub-Saharan Africa where access to care and antiretroviral therapy remains limited and advanced immunodeficiency, poverty and malnutrition remains the norm. As a zoonotic disease, environmental outbreaks of both human and animal cryptococcosis have been reported, possibly driven by climate change. This is best exemplified by the resurgence of C. gattii infection in Vancouver Island, Canada, and the Pacific Northwest of the United States since 1999. Here we describe how the colliding epidemics of HIV, transplantation and immunologics, climate change and migration have contributed to the rise of cryptococcosis. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
Open AccessReview
Masking the Pathogen: Evolutionary Strategies of Fungi and Their Bacterial Counterparts
J. Fungi 2015, 1(3), 397-421; https://doi.org/10.3390/jof1030397 - 10 Dec 2015
Cited by 2
Abstract
Pathogens reduce immune recognition of their cell surfaces using a variety of inert structural polysaccharides. For example, capsular polysaccharides play critical roles in microbial survival strategies. Capsules are widely distributed among bacterial species, but relatively rare in eukaryotic microorganisms, where they have evolved [...] Read more.
Pathogens reduce immune recognition of their cell surfaces using a variety of inert structural polysaccharides. For example, capsular polysaccharides play critical roles in microbial survival strategies. Capsules are widely distributed among bacterial species, but relatively rare in eukaryotic microorganisms, where they have evolved considerable complexity in structure and regulation and are exemplified by that of the HIV/AIDS-related fungus Cryptococcus neoformans. Endemic fungi that affect normal hosts such as Histoplasma capsulatum and Blastomyces dermatitidis have also evolved protective polysaccharide coverings in the form of immunologically inert α-(1,3)-glucan polysaccharides to protect their more immunogenic β-(1,3)-glucan-containing cell walls. In this review we provide a comparative update on bacterial and fungal capsular structures and immunogenic properties as well as the polysaccharide masking strategies of endemic fungal pathogens. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
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Open AccessReview
Pushing the Limits of MALDI-TOF Mass Spectrometry: Beyond Fungal Species Identification
J. Fungi 2015, 1(3), 367-383; https://doi.org/10.3390/jof1030367 - 16 Oct 2015
Cited by 8
Abstract
Matrix assisted laser desorption ionization time of flight (MALDI-TOF) is a powerful analytical tool that has revolutionized microbial identification. Routinely used for bacterial identification, MALDI-TOF has recently been applied to both yeast and filamentous fungi, confirming its pivotal role in the rapid and [...] Read more.
Matrix assisted laser desorption ionization time of flight (MALDI-TOF) is a powerful analytical tool that has revolutionized microbial identification. Routinely used for bacterial identification, MALDI-TOF has recently been applied to both yeast and filamentous fungi, confirming its pivotal role in the rapid and reliable diagnosis of infections. Subspecies-level identification holds an important role in epidemiological investigations aimed at tracing virulent or drug resistant clones. This review focuses on present and future applications of this versatile tool in the clinical mycology laboratory. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
Open AccessReview
Candida glabrata, Friend and Foe
J. Fungi 2015, 1(2), 277-292; https://doi.org/10.3390/jof1020277 - 16 Sep 2015
Cited by 2
Abstract
Candida glabrata is mostly good, but, at times, it is an opportunistic pathogen. Previously known as Torulopsis glabrata, it enjoyed a good reputation and was even present in starter cultures. Its haploid genome and lack of mating made it an attractive challenge [...] Read more.
Candida glabrata is mostly good, but, at times, it is an opportunistic pathogen. Previously known as Torulopsis glabrata, it enjoyed a good reputation and was even present in starter cultures. Its haploid genome and lack of mating made it an attractive challenge for yeast genetics studies. However, more recently it has become better known due to its character as an emerging cause of candidiasis, and for its resistance to multidrugs that are employed for candidiasis treatment. While now classified as Candida glabrata, it is still not a good fit and tends to stand alone as a very unique yeast. In terms of sequence, it is dissimilar to other Candida yeast and most similar to Saccharomyces cerevisiae. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
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Application of Culture-Independent Rapid Diagnostic Tests in the Management of Invasive Candidiasis and Cryptococcosis
J. Fungi 2015, 1(2), 217-251; https://doi.org/10.3390/jof1020217 - 31 Aug 2015
Cited by 5
Abstract
The diagnosis of invasive candidiasis (IC) and cryptococcosis is often complicated by slow and insensitive culture-based methods. Such delay results in poor outcomes due to the lack of timely therapeutic interventions. Advances in serological, biochemical, molecular and proteomic approaches have made a favorable [...] Read more.
The diagnosis of invasive candidiasis (IC) and cryptococcosis is often complicated by slow and insensitive culture-based methods. Such delay results in poor outcomes due to the lack of timely therapeutic interventions. Advances in serological, biochemical, molecular and proteomic approaches have made a favorable impact on this process, improving the timeliness and accuracy of diagnosis with resultant improvements in outcome. This paper will serve as an overview of recent developments in the diagnostic approaches to infections due to these important yeast-fungi. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
Open AccessReview
Is Cryptococcus gattii a Primary Pathogen?
J. Fungi 2015, 1(2), 154-167; https://doi.org/10.3390/jof1020154 - 29 Jul 2015
Cited by 13Correction
Abstract
The two etiologic agents of cryptococcal meningoencephalitis, Cryptococcus neoformans and C. gattii, have been commonly designated as either an opportunistic pathogen for the first species or as a primary pathogen for the second species. Such a distinction has been based on epidemiological [...] Read more.
The two etiologic agents of cryptococcal meningoencephalitis, Cryptococcus neoformans and C. gattii, have been commonly designated as either an opportunistic pathogen for the first species or as a primary pathogen for the second species. Such a distinction has been based on epidemiological findings that the majority of patients presenting meningoencephalitis caused by C. neoformans are immunocompromised while C. gattii infection has been reported more often in immunocompetent patients. A recent report, however, showed that GM-CSF (granulocyte-macrophage colony-stimulating factor) neutralizing antibodies were prevalent in the plasma of “apparently immunocompetent” C. gattii patients with meningoencephalitis. Because GM-CSF is essential for differentiation of monocytes to macrophages and modulating the immune response, it is not surprising that the lack of GM-CSF function predisposes otherwise healthy individuals to infection via inhalation of environmental pathogens such as C. gattii. Since the test for anti-GM-CSF autoantibodies is not included in routine immunological profiling at most hospitals, healthy patients with GM-CSF neutralizing antibodies are usually categorized as immunocompetent. It is likely that a comprehensive immunological evaluation of patients with C. gattii meningoencephalitis, who had been diagnosed as immunocompetent, would reveal a majority of them had hidden immune dysfunction. This paper reviews the relationship between GM-CSF neutralizing antibodies and the risk for C. gattii infection with CNS involvement. Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
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Open AccessCorrection
Correction: Kwon-Chung, K.J. et al. Is Cryptococcus gattii a Primary Pathogen? J. Fungi 2015, 1, 154–167
J. Fungi 2016, 2(3), 20; https://doi.org/10.3390/jof2030020 - 05 Jul 2016
Abstract
The authors of the published paper [1] would like to correct Table 1.[...] Full article
(This article belongs to the Special Issue Yeasts Are Beasts)
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