Pathogenic fungi are

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...

that cause disease in humans or other

organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells ( cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fu ...

s. Approximately 300 fungi are known to be pathogenic to humans. Markedly more fungi are known to be pathogenic to

plant Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae excl ...

life than those of the animal kingdom. The study of fungi pathogenic to humans is called "medical mycology". Although fungi are

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

, many pathogenic fungi are

microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...

s. The study of fungi and other organisms pathogenic to plants is called

plant pathology Plant pathology (also phytopathology) is the scientific study of diseases in plants caused by pathogens (infectious organisms) and environmental conditions (physiological factors). Organisms that cause infectious disease include fungi, ...

''Candida''

''Candida'' species cause infections in individuals with deficient immune systems. Th1-type

cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines ...

(CMI) is required for clearance of a fungal infection. ''

Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...

'' is a kind of diploid

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

that commonly occurs among the human

gut microflora Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut mi ...

. ''C. albicans'' is an opportunistic pathogen in humans. Abnormal over-growth of this fungus can occur, particularly in

immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...

individuals. ''C. albicans'' has a

parasexual cycle The parasexual cycle, a process restricted to fungi and single-celled organisms, is a nonsexual mechanism of parasexuality for transferring genetic material without meiosis or the development of sexual structures. It was first described by Italian ...

that appears to be stimulated by environmental stress. Other species of ''Candida'' may be pathogenic as well, including ''

Candida stellatoidea ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...

, C. tropicalis, C. pseudotropicalis, C. krusei, C. parapsilosis,'' and '' C. guilliermondii.''

''Aspergillus''

The most common pathogenic species are ''

Aspergillus fumigatus ''Aspergillus fumigatus'' is a species of fungus in the genus '' Aspergillus'', and is one of the most common ''Aspergillus'' species to cause disease in individuals with an immunodeficiency. ''Aspergillus fumigatus'', a saprotroph widespread i ...

'' and ''

Aspergillus flavus ''Aspergillus flavus'' is a saprotrophic and pathogenic fungus with a cosmopolitan distribution. It is best known for its colonization of cereal grains, legumes, and tree nuts. Postharvest rot typically develops during harvest, storage, and/or ...

''. Aspergillus flavus produces

aflatoxin Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly ''Aspergillus'' species. The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, sweetcorn ...

which is both a toxin and a

carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...

and which can potentially contaminate foods such as nuts. ''Aspergillus fumigatus'' and '' Aspergillus clavatus'' can cause

allergic Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic der ...

disease. Some ''Aspergillus'' species cause disease on grain crops, especially

maize Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American English, North American and Australian English), is a cereal grain first domesticated by indigenous peoples of Mexico, indigenous ...

, and synthesize

mycotoxin A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...

s including

Aspergillosis Aspergillosis is a fungal infection of usually the lungs, caused by the genus ''Aspergillus'', a common mould that is breathed in frequently from the air around, but does not usually affect most people. It generally occurs in people with lung dis ...

is the group of diseases caused by ''Aspergillus''. The symptoms include fever, cough, chest pain or breathlessness. Usually, only patients with weakened

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

s or with other

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...

conditions are susceptible. The spores of ''

'' are ubiquitous in the atmosphere. ''A. fumigatus'' is an opportunistic pathogen. It can cause potentially lethal invasive infection in immunocompromised individuals. ''A. fumigatus'' has a fully functional sexual cycle that produces cleistothecia and

ascospores An ascus (; ) is the sexual spore-bearing cell produced in ascomycete fungi. Each ascus usually contains eight ascospores (or octad), produced by meiosis followed, in most species, by a mitotic cell division. However, asci in some genera or ...

''Cryptococcus''

Cryptococcus neoformans ''Cryptococcus neoformans'' is an encapsulated yeast belonging to the class Tremellomycetes and an obligate aerobe that can live in both plants and animals. Its teleomorph is a filamentous fungus, formerly referred to ''Filobasidiella neoformans ...

'' can cause a severe form of

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...

and meningo-encephalitis in patients with HIV infection and

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...

. The majority of ''Cryptococcus'' species live in the soil and do not cause disease in humans. ''

'' is the major human and animal pathogen. ''

Papiliotrema laurentii ''Papiliotrema laurentii'' (synonym ''Cryptococcus laurentii'') is a species of fungus in the family Rhynchogastremaceae. It is typically isolated in its yeast state. In its yeast state, it is a rare human pathogen, able to provoke a skin conditi ...

'' and ''

Naganishia albida ''Naganishia albida'' (synonym ''Cryptococcus albidus'') is a species of fungus in the family Filobasidiaceae. It is currently only known from its yeast state. The species was originally isolated from the air in Japan, and has subsequently been ...

'', both formerly referred to ''

Cryptococcus ''Cryptococcus'' is a genus of fungi in the family Cryptococcaceae that includes both yeasts and filamentous species. The filamentous, sexual forms or teleomorphs were formerly classified in the genus ''Filobasidiella'', while ''Cryptococcus'' ...

'', have been known to occasionally cause moderate-to-severe disease in human patients with compromised immunity. '' Cryptococcus gattii'' is endemic to tropical parts of the continent of Africa and Australia and can cause disease in non-immunocompromised people. Infecting ''C. neoformans'' cells are usually phagocytosed by

alveolar macrophage An alveolar macrophage, pulmonary macrophage, (or dust cell) is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls. Activity of the alveolar macropha ...

s in the lung. The invading '' C. neoformans'' cells may be killed by the release of oxidative and nitrosative molecules by these macrophages. However some ''C. neoformans'' cells may survive within the macrophages. The ability of the pathogen to survive within the macrophages probably determines latency of the disease, dissemination and resistance to

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

agents. In order to survive in the hostile intracellular environment of the macrophage, one of the responses of ''C. neoformans'' is to

upregulate In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pro ...

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s employed in responses to

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

. The haploid nuclei of ''C. neoformans'' can undergo nuclear fusion ( karyogamy) to become diploid. These diploid nuclei may then undergo

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately ...

, including recombination, resulting in the formation of haploid

basidiospore A basidiospore is a reproductive spore produced by Basidiomycete fungi, a grouping that includes mushrooms, shelf fungi, rusts, and smuts. Basidiospores typically each contain one haploid nucleus that is the product of meiosis, and they are ...

s that are able to disperse. Meiosis may facilitate

repair The technical meaning of maintenance involves functional checks, servicing, repairing or replacing of necessary devices, equipment, machinery, building infrastructure, and supporting utilities in industrial, business, and residential installa ...

of ''C. neoformans'' DNA in response to macrophage challenge.

''Histoplasma''

'' Histoplasma capsulatum'' can cause histoplasmosis in humans, dogs and cats. The fungus is most prevalent in the Americas, India and southeastern Asia. It is endemic in certain areas of the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

. Infection is usually due to inhaling contaminated air.

''Pneumocystis''

Pneumocystis jirovecii ''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. P ...

'' (or Pneumocystis carinii) can cause a form of

pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severit ...

in people with weakened

s, such as premature children, the elderly and

patients.

''Stachybotrys''

Stachybotrys chartarum ''Stachybotrys chartarum'' (, ), also known as black mold or toxic black mold, is a species of microfungus that produces its conidia in slime heads. It is sometimes found in soil and grain, but the mold is most often detected in cellulose-rich b ...

'' or "black mold" can cause respiratory damage and severe headaches. It frequently occurs in houses and in regions that are chronically damp.

Host defense mechanisms

Endothermy

Mammalian

endotherm An endotherm (from Greek ἔνδον ''endon'' "within" and θέρμη ''thermē'' "heat") is an organism that maintains its body at a metabolically favorable temperature, largely by the use of heat released by its internal bodily functions inst ...

y and homeothermy are potent nonspecific defenses against most fungi. A comparative genomic study found that in opportunistic fungi there are few if any specialised virulence traits consistently linked to opportunistic pathogenicity of fungi in humans apart from the ability to grow at 37 °C.

Barrier tissues

The

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to ...

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

, and the genital-urinary tract induced inflammation are common bodily regions of fungal infection.

Immune response

Studies have shown that hosts with higher levels of immune response cells such as

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

s/ macrophages, dendritic cells, and invariant natural killer (iNK) T-cells exhibited greater control of fungal growth and protection against systemic infection.

Pattern recognition receptor Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of ...

s (PRRs) play an important role in inducing an immune response by recognizing specific fungal pathogens and initiating an immune response. In the case of mucosal

candidiasis Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...

, the cells that produce cytokine IL-17 are extremely important in maintaining

innate immunity The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

Link to extremotolerance

A comprehensive comparison of distribution of

opportunistic pathogens An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...

and stress-tolerant fungi in the fungal tree of life showed that polyextremotolerance and opportunistic pathogenicity consistently appear in the same fungal orders and that the co-occurrence of opportunism and extremotolerance (e.g. osmotolerance and psychrotolerance) is statistically significant. This suggests that some adaptations to stressful environments may also promote fungal survival during the infection.

References

External links

Ecmm.eu: Official European Confederation of Medical Mycology website
{{Fungi classification, state=collapsed . Fungi and humans Fungus common names Mycology