Fungal allergy - fungal ecology in dwelling environments]

Fungi related to allergies are commonly found in dwelling environments. The predominant fungi Cladosporium, Penicillium, Aspergillus, Alternaria, Wallemia and Rhodotorula live mainly in indoor air, house dust (HD), futons, clothes and contaminated building materials. Fungi in HD are especially important allergens. The fungal CFU and predominant fungi in HD are 10(4) - 10(6)/g and are composed of xerophilic or osmophilic species Aspergillus restrictus, Wallemia and Eurotium but not many yeasts and actinomycetes. Fungal contamination of materials is a serious human health problem because the fungal cells scatter from the materials in the air or HD. The biological activities by fungi also have health implications from the viewpoint of fungal allergens. In this paper, fungal germination, enzyme activities, contaminating cell form and viable or nonviable cells are also discussed.     

Our Current Understanding of Fungal Biofilms

Fungal biofilms are an escalating clinical problem associated with significant rates of mortality. Candida albicans is the most notorious of all fungal biofilm formers. However, non-Candida species, yeasts such as Cryptococcus neoformans, and filamentous moulds such as Aspergillus fumigatus, have been shown to be implicated in biofilm-associated infections. Fungal biofilms have distinct developmental phases, including adhesion, colonisation, maturation and dispersal, which are governed by complex molecular events. Recalcitrance to antifungal therapy remains the greatest threat to patients with fungal biofilms. This review discusses our current understanding of the basic biology and clinical implications associated with fungal biofilms.     

Developments in Fungal Taxonomy

Fungal infections, especially those caused by opportunistic species, have become substantially more common in recent decades. Numerous species cause human infections, and several new human pathogens are discovered yearly. This situation has created an increasing interest in fungal taxonomy and has led to the development of new methods and approaches to fungal biosystematics which have promoted important practical advances in identification procedures. However, the significance of some data provided by the new approaches is still unclear, and results drawn from such studies may even increase nomenclatural confusion. Analyses of rRNA and rDNA sequences constitute an important complement of the morphological criteria needed to allow clinical fungi to be more easily identified and placed on a single phylogenetic tree. Most of the pathogenic fungi so far described belong to the kingdom Fungi; two belong to the kingdom Chromista. Within the Fungi, they are distributed in three phyla and in 15 orders (Pneumocystidales, Saccharomycetales, Dothideales, Sordariales, Onygenales, Eurotiales, Hypocreales, Ophiostomatales, Microascales, Tremellales, Poriales, Stereales, Agaricales, Schizophyllales, and Ustilaginales).     

Fungal allergens.

Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immunotherapy of allergy to fungi require well-characterized or standardized extracts that contain the relevant allergen(s) of the appropriate fungus. Production of standardized extracts is difficult since fungal extracts are complex mixtures and a variety of fungi are allergenic. Thus, the currently available extracts are largely nonstandardized, even uncharacterized, crude extracts. Recent significant progress in isolating and characterizing relevant fungal allergens is summarized in the present review. Particularly, some allergens from the genera Alternaria, Aspergillus, and Cladosporium are now thoroughly characterized, and allergens from several other genera, including some basidiomycetes, have also been purified. The availability of these extracts will facilitate definitive studies of fungal allergy prevalence and immunotherapy efficacy as well as enhance both the diagnosis and therapy of fungal allergy.     

Fungal allergy -clinical aspect-]

Fungus is known to be one of the important causative allergens of allergic diseases such as bronchial asthma, allergic rhinitis and atopic dermatitis. Not only outdoor airborne fungi but also indoor fungi such as Aspergillus restrictus and Eurotium have recently received attention as causative fungal allergens of allergic diseases. In addition to careful history taking, in vivo testing methods such as skin test and conjunctival or bronchial provocation tests are sometimes necessary to diagnose the causative allergen. Problems requiring resolution are: 1. fungal allergens composed of multiple allergenic components, 2. difficulty of environmental monitoring of fungal allergens, 3. special characteristics as microorganisms, and 4. characteristics of normal flora allergy, etc.     

Immunotherapy of Fungal Infections

Fungal organisms are ubiquitous in the environment. Pathogenic fungi, although relatively few in the whole gamut of microbial pathogens, are able to cause disease with varying degrees of severity in individuals with normal or impaired immunity. The disease state is an outcome of the fungal pathogen’s interactions with the host immunity, and therefore, it stands to reason that deep/invasive fungal diseases be amenable to immunotherapy. Therefore, antifungal immunotherapy continues to be attractive as an adjunct to the currently available antifungal chemotherapy options for a number of reasons, including the fact that existing antifungal drugs, albeit largely effective, are not without limitations, and that morbidity and mortality associated with invasive mycoses are still unacceptably high. For several decades, intense basic research efforts have been directed at development of fungal immunotherapies. Nevertheless, this approach suffers from a severe bench-bedside disconnect owing to several reasons: the chemical and biological peculiarities of the fungal antigens, the complexities of host-pathogen interactions, an under-appreciation of the fungal disease landscape, the requirement of considerable financial investment to bring these therapies to clinical use, as well as practical problems associated with immunizations. In this general, non-exhaustive review, we summarize the features of ongoing research efforts directed towards devising safe and effective immunotherapeutic options for mycotic diseases, encompassing work on antifungal vaccines, adoptive cell transfers, cytokines, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), and other agents.     

Fungal Diversity and Use in Decomposition of Environmental Pollutants

This article presents a critical review of the actual state of fungal activities on environmental pollutants, fungal diversity, the use of fungi in the degradation of chemical pollutants, enzyme degrading systems and perspectives on the use of fungi in bioremediation and unexplored research. The ability of fungi to transform or metabolize chemical pollutants has received much attention due to environmental persistence and chemical toxicity. The fungal degradation of xenobiotics is looked upon as an effective method of removing these pollutants from the environment by a process which is currently known as bioremediation. This review summarizes information from fundamental works that have revealed that a wide variety of fungi are capable of degrading an equally wide range of toxical chemical. The capacity of non-ligninolytic and ligninolytic fungi in the bioremediation of polycyclic aromatic hydrocarbon (PAHs), benzene-toluene-ethylbenzene-xylene (BTEX), chlorophenols, polychlorinated biphenyl, munitions waste and pesticides have been discussed. Besides this, several extracellular enzymes are involved in the metabolism of xenobiotic compounds as well as other factors related to these processes.     

Fungal diversity and use in decomposition of environmental pollutants

This article presents a critical review of the actual state of fungal activities on environmental pollutants, fungal diversity, the use of fungi in the degradation of chemical pollutants, enzyme degrading systems and perspectives on the use of fungi in bioremediation and unexplored research. The ability of fungi to transform or metabolize chemical pollutants has received much attention due to environmental persistence and chemical toxicity. The fungal degradation of xenobiotics is looked upon as an effective method of removing these pollutants from the environment by a process which is currently known as bioremediation. This review summarizes information from fundamental works that have revealed that a wide variety of fungi are capable of degrading an equally wide range of toxical chemical. The capacity of non-ligninolytic and ligninolytic fungi in the bioremediation of polycyclic aromatic hydrocarbon (PAHs), benzene-toluene-ethylbenzene-xylene (BTEX), chlorophenols, polychlorinated biphenyl, munitions waste and pesticides have been discussed. Besides this, several extracellular enzymes are involved in the metabolism of xenobiotic compounds as well as other factors related to these processes.     

Fungal spoilage of foods and its risk assessment]

From the second half of the 1990s, an increased regard has been given to the fungal spoilage of foods as follows: 1) post-harvest diseases and losses of fruits and vegetables, 2) deterioration of low water activity foods by xerophilic fungi, 3) contamination of psychrotolerant or psychrophilic fungi on foodstuffs and processed foods during storage and distribution at low temperature, and 4) spoilage of heat processed foods and soft drinks by heat-resistant fungi. In accordance with an international concern about food safety, mycotoxin contamination of foods has gained much global attention in recent times owing to its potential health hazards. The evaluation of mycotoxin hazards is principally based on the determination of a no-observed effect level (NOEL) in long-term toxicological studies, and the application of a safety factor (usually 100). In addition to hazard assessment, data on the natural occurrence of mycotoxins in various commodities and food intake data are needed to enable exposure assessment. Thus risk assessment of mycotoxins is, in fact, the product of hazard assessment and exposure assessment. In 1997, the FAO/WHO Joint Expert Committee on Food Additives (JECFA) considered estimates of the carcinogenic potency of aflatoxins and the potential risks associated with their intake. Recently the Codex Alimentarius Commission (Codex) has established standards for aflatoxin M1 in milk and for patulin in apple juice. The Codex is an international organization, supported by FAO/WHO, aiming at facilitating world trade and protecting the health of the consumer by developing international standards for food and feeds. Apart from aflatoxins, the JECFA has measured a provisional tolerable daily intake (TDI) for ochratoxin A, patulin, deoxynivalenol, T-2/HT-2 toxins, zearalenone and fumonisins. In 2001, the mycotoxins evaluated or re-evaluated at the JECFA meeting included ochratoxin A, deoxynivalenol, T-2/HT-2 toxins, fumonisins, and aflatoxin M1. In Japan, specific regulations now exist for deoxynivalenol (1.1 ppm) in wheat grains and for patulin (50 ppb) in apple juice and its products.     

Genomics of the fungal kingdom: insights into eukaryotic biology

The last decade has witnessed a revolution in the genomics of the fungal kingdom. Since the sequencing of the first fungus in 1996, the number of available fungal genome sequences has increased by an order of magnitude. Over 40 complete fungal genomes have been publicly released with an equal number currently being sequenced--representing the widest sampling of genomes from any eukaryotic kingdom. Moreover, many of these sequenced species form clusters of related organisms designed to enable comparative studies. These data provide an unparalleled opportunity to study the biology and evolution of this medically, industrially, and environmentally important kingdom. In addition, fungi also serve as model organisms for all eukaryotes. The available fungal genomic resource, coupled with the experimental tractability of the fungi, is accelerating research into the fundamental aspects of eukaryotic biology. We provide here an overview of available fungal genomes and highlight some of the biological insights that have been derived through their analysis. We also discuss insights into the fundamental cellular biology shared between fungi and other eukaryotic organisms.     

Fungal stealth technology

Medically important fungi range from commensal organisms that cause opportunistic infections to primary fungal pathogens that can cause disease in immunocompetent hosts. Host phagocyte-expressed pattern-recognition receptors represent one obstacle to infection, and the extent to which fungal cells can evade detection by host receptors helps shape their pathogenic potential. This review highlights recently defined mechanisms employed by successful fungal pathogens to conceal their immunostimulatory molecular signatures from leukocyte receptors or to disrupt host response signals. Continued improvements in our understanding of these fungal stealth mechanisms should provide new options for future therapeutics to expose these fungal pathogens and limit their virulence capacity.     

Fungal contamination of elementary schools: a new environmental hazard.

BACKGROUND: Sensitivity to fungi is a significant cause of allergic diseases, and prolonged indoor exposure to fungi is a growing health concern. OBJECTIVE: This study evaluates the health effects of mold-contaminated schools on students and teachers. A discussion of the effectiveness of current methods for evaluating these schools, with a focus on the importance of using total mold spore counts, is also provided. METHODS: Two Connecticut public schools were tested using multiple air quality testing methods, with the standard for a healthy indoor environment being total mold spore counts lower than 1,000 spores/m3. The health impact of the mold exposure at each school was evaluated using the validated Rhinitis Outcomes Questionnaire. RESULTS: The testing of the first school found indoor mold counts ranging from 6,000 to 50,000 spores/m3. Eighty-five of the students and teachers reported significant allergic symptoms to the school nurse. This school is currently being demolished. More than 2 years after the exposure ended, a number of occupants of the school continue to have elevated symptoms compared with before their exposure to the school. The testing of the second school revealed total mold spore counts ranging between 2,000 and 9,000 spores/m3, qualifying it an unhealthy environment in need of immediate remediation. Students reported significant allergic symptoms from exposure to certain rooms that are currently being remediated. CONCLUSIONS: Because of the negative impact on health that indoor mold exposure has, particularly in atopic patients, schools should be routinely tested for fungal contamination. Total mold spore counts should be performed using volumetric air sampling such as the Allergenco MK-3 (Allergenco, San Antonio, TX) because testing air quality via semiquantitative culture sampling alone does not give a true reflection of the extent of fungal contamination. Finally, the standard for a healthy indoor environment should be defined as having <1,000 spores/m3.     

Fungal diseases: an evolving public health challenge.

The emergence of new fungal pathogens and the resurgence of mycotic diseases that had previously been uncommon is a serious and growing public health problem. This review examines the factors involved in the emergence or re-emergence of several mycotic diseases, including coccidioidomycosis and cryptococcosis, over the past two decades. New approaches to prevention and control are also discussed.     

Fungal Sex and Pathogenesis

Summary: Human fungal pathogens are associated with diseases ranging from dandruff and skin colonization to invasive bloodstream infections. The major human pathogens belong to the Candida, Aspergillus, and Cryptococcus clades, and infections have high and increasing morbidity and mortality. Many human fungal pathogens were originally assumed to be asexual. However, recent advances in genome sequencing, which revealed that many species have retained the genes required for the sexual machinery, have dramatically influenced our understanding of the biology of these organisms. Predictions of a rare or cryptic sexual cycle have been supported experimentally for some species. Here, I examine the evidence that human pathogens reproduce sexually. The evolution of the mating-type locus in ascomycetes (including Candida and Aspergillus species) and basidiomycetes (Malassezia and Cryptococcus) is discussed. I provide an overview of how sex is suppressed in different species and discuss the potential associations with pathogenesis.     

Fungal recognition by mammalian fibrinogen-related proteins

Fungi are ubiquitous eukaryotic micro-organisms present in virtually all environmental habitats. Although rarely pathogenic to the healthy population, many fungal species are capable of causing human disease in immunocompromised individuals. Thus, fungal infections remain a significant cause of morbidity and mortality, with rising prevalence accompanying the worldwide increase in immunosuppression-based therapies. Therefore, better understanding of the mutual interactions between the protective host mechanisms and the invading fungi remains of critical importance. The innate immune system constitutes the first line of defence against exogenous insults. The innate antifungal immunity is mediated through recognition of specific pathogen-associated molecular patterns (PAMPs) by a broad panel of host pattern recognition receptors (PRRs), responsible for mounting adequate protective responses. In this review, we describe fungal PAMPs as well as a selection of PRRs able to recognize them. We focus on the members of the fibrinogen-related domain (FReD) protein family that have been shown to recognize fungi-derived molecules: ficolins, fibrinogen C domain containing 1 (FIBCD1) and tenascin-C. We describe their structure, their binding targets and their established as well as putative biological functions related to fungal recognition and immunity.     

Fungal endophytes as prolific source of phytochemicals and other bioactive natural products: A review

Endophytic fungi are those that live internally in apparently healthy and asymptomatic hosts. Endophytic fungi appear to be ubiquitous; indeed, no study has yet shown the existence of a plant species without endophytes. High species diversity is another characteristic of endophytic mycobiota which is depicted by the fact that it is quite common for endophyte surveys to find assemblages consisting of more than 30 fungal species per host plant species. Medicinal plants had been used to isolate and characterize directly the bioactive metabolites. However, the discovery of fungal endophytes inside these plants with capacity to produce the same compounds shifted the focus of new drug sources from plants to fungi. Bioactive natural products from endophytic fungi, isolated from different plant species, are attracting considerable attention from natural product chemists and biologists alike which is clearly depicted by the steady increase of publications devoted to this topic during the recent years. This review will highlight the chemical potential of endophytic fungi with focus on the detection of pharmaceutically valuable plant constituents as products of fungal biosynthesis. In addition, it will cover newly discovered endophytic fungi and also new bioactive metabolites reported in recent years from fungal endophytes. It summarizes the up-to-date and comprehensive information on bioactive compounds from endophytic fungi by having done a thorough survey of literature.     

Fungal contamination of bedding

BACKGROUND: It is currently believed that most fungal exposure occurs external to the home. AIMS: To enumerate the fungal flora of used synthetic and feather pillows and the dust vacuumed from them, in the UK. METHODS: 10 pillows aged between 1.5 and >20 years in regular use were collected and quantitatively cultured for fungi. Swatches were taken from nine sections of the pillow and dust was also collected by vacuum from five pillows. Pillow vacuuming was carried out prior to pillow culture. All were cultured at room temperature, 30 and 37 degrees C for 7 days in broth before plating, and a subset were also cultured for 24 h in broth and then plated. Fungi were identified by standard morphological methods. RESULTS: The commonest three species isolated were Aspergillus fumigatus (n = 10), Aureobasidium pullulans (n = 6) and Rhodotorula mucilaginosa (n = 6). Another 47 species were isolated from pillows and vacuum dust. The number of species isolated per pillow varied from 4 to 16, with a higher number from synthetic pillows. Compared with the nonallergenic A. pullulans, more A. fumigatus was found in synthetic than feather pillows. CONCLUSIONS: We have examined pillows for fungal contamination, and show that the typical used pillow contains a substantial load of many species of fungi, particularly A. fumigatus. Given the time spent sleeping, and the proximity of the pillow to the airway, synthetic and feather pillows could be the primary source of fungi and fungal products. This has important implications for patients with respiratory disease, and especially asthma and sinusitis.     

The Evolutionary Biology and Population Genetics Underlying Fungal Strain Typing

Strain typing of medically important fungi and fungal population genetics have been stimulated by new methods of tapping DNA variation. The aim of this contribution is to show how awareness of fungal population genetics can increase the utility of strain typing to better serve the interests of medical mycology. Knowing two basic features of fungal population biology, the mode of reproduction and genetic differentiation or isolation, can give medical mycologists information about the intraspecific groups that are worth identifying and the number and type of markers that would be needed to do so. The same evolutionary information can be just as valuable for the selection of fungi for development and testing of pharmaceuticals or vaccines. The many methods of analyzing DNA variation are evaluated in light of the need for polymorphic loci that are well characterized, simple, independent, and stable. Traditional population genetic and new phylogenetic methods for analyzing mode of reproduction, genetic differentiation, and isolation are reviewed. Strain typing and population genetic reports are examined for six medically important species: Coccidioides immitis, Histoplasma capsulatum, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and A. flavus. Research opportunities in the areas of genomics, correlation of clinical variation with genetic variation, amount of recombination, and standardization of approach are suggested.     

Fungal infections in immunocompromised patients]

The number of immunocompromised patients is increasing due to the intensive therapy being administered those with cancer, organ transplant, and HIV infection. Fungal infections are one of the important opportunistic infections in immunocompromised patients. Early diagnosis is difficult, and the prognosis of these patinas is usually poor. Several methods of diagnosis for fungal infections have been developed: detection of antigens of the infected fungi from the sera is useful for early diagnosis; polymerase chain reaction (PCR) technology may be the most valuable method for the diagnosis of fungal infection in immunocompromised patients, and antifungal agents are the drugs used to the fungal infections in those patients. However, there are only five drugs available to fungal infections in Japan. Although amphotericin B is the recommended first choice for treatment of invasive aspergillosis, its use for immunocompromised patients is limited because of its adverse effects. Novel antifungal agents (azoles, amphotericin B drug deliver system, and 1,3-beta-D-glucan synthetase inhibitors) have been developed and some of these compounds undergoing clinical trials.