Pathogenic fungus

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Pathogenic fungi are fungi that cause disease in humans or other organisms. Although fungi are eukaryotic, many pathogenic fungi are microorganisms. [1] Approximately 300 fungi are known to be pathogenic to humans; [2] their study is called "medical mycology". Fungal infections are estimated to kill more people than either tuberculosis or malaria—about two million people per year. [3]

Contents

In 2022 the World Health Organization (WHO) published a list of fungal pathogens which should be a priority for public health action. [4]

Markedly more fungi are known to be pathogenic to plant life than those of the animal kingdom. [5] The study of fungi and other organisms pathogenic to plants is called plant pathology.

Pathogens of particular concern

According to the World Health Organization (WHO) in 2022 pathogens of particular concern are: [4]

Critical priority
Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, Candida albicans.
High priority
Nakaseomyces glabrata (Candida glabrata), Histoplasma spp., eumycetoma causative agents, Mucorales, Fusarium spp., Candida tropicalis,Candida parapsilosis.
Medium priority
Scedosporium spp., Lomentospora prolificans, Coccidioides spp., Pichia kudriavzeveii (Candida krusei), Cryptococcus gattii, Talaromyces marneffei, Pneumocystis jirovecii, Paracoccidioides spp.

Candida

Candida. Pap test specimen. Pap stain. Candida pap 1.jpg
Candida. Pap test specimen. Pap stain.

Candida species cause infections in individuals with deficient immune systems. Candida species tend to be the culprit of most fungal infections and can cause both systemic and superficial infection. [6] Th1-type cell-mediated immunity (CMI) is required for clearance of a fungal infection. Candida albicans is a kind of diploid yeast that commonly occurs among the human gut microflora. C. albicans is an opportunistic pathogen in humans. Abnormal over-growth of this fungus can occur, particularly in immunocompromised individuals. [7] C. albicans has a parasexual cycle that appears to be stimulated by environmental stress. [8]

C. auris , first described in 2009, is resistant to many frontline antifungal drugs, disinfectants, and heat, which makes it extremely difficult to eradicate. Like many fungal pathogens it mostly affects immunocompromised people; if in the blood or other organs and tissues, mortality is about 50%. [3]

Other species of Candida may be pathogenic as well, including Candida stellatoidea, C. tropicalis, C. pseudotropicalis, C. krusei, C. parapsilosis, and C. guilliermondii. [9]

Aspergillus

Aspergillosis. H&E stain. Pulmonary aspergillosis.jpg
Aspergillosis. H&E stain.

The most common pathogenic species are Aspergillus fumigatus and Aspergillus flavus . Aspergillus flavus produces aflatoxin which is both a toxin and a carcinogen and which can potentially contaminate foods such as nuts. Aspergillus fumigatus and Aspergillus clavatus can cause allergic disease. Some Aspergillus species cause disease on grain crops, especially maize, and synthesize mycotoxins including aflatoxin. Aspergillosis is the group of diseases caused by Aspergillus. The symptoms include fever, cough, chest pain or breathlessness. Usually, only patients with weakened immune systems or with other lung conditions are susceptible. [1]

The spores of Aspergillus fumigatus are ubiquitous in the atmosphere. A. fumigatus is an opportunistic pathogen. It can cause potentially lethal invasive infection in immunocompromised individuals. [10] A. fumigatus has a fully functional sexual cycle that produces cleistothecia and ascospores.[ citation needed ]

Cryptococcus

Cryptococcus. FNA specimen. Field stain. Cryptococcus.jpg
Cryptococcus. FNA specimen. Field stain.

Cryptococcus neoformans can cause a severe form of meningitis and meningo-encephalitis in patients with HIV infection and AIDS. The majority of Cryptococcus species live in the soil and do not cause disease in humans. Cryptococcus neoformans is the major human and animal pathogen. Papiliotrema laurentii and Naganishia albida , both formerly referred to 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. [1]

Infecting C. neoformans cells are usually phagocytosed by alveolar macrophages in the lung. [11] The invading C. neoformans cells may be killed by the release of oxidative and nitrosative molecules by these macrophages. [12] However some C. neoformans cells may survive within the macrophages. [11] The ability of the pathogen to survive within the macrophages probably determines latency of the disease, dissemination and resistance to antifungal agents. In order to survive in the hostile intracellular environment of the macrophage, one of the responses of C. neoformans is to upregulate genes employed in responses to oxidative stress. [11]

The haploid nuclei of C. neoformans can undergo nuclear fusion (karyogamy) to become diploid. These diploid nuclei may then undergo meiosis, including recombination, resulting in the formation of haploid basidiospores that are able to disperse. [13] Meiosis may facilitate repair of C. neoformans DNA in response to macrophage challenge. [13] [14]

Histoplasma

Histoplasmosis. PASD stain. Histoplasma pas-d.jpg
Histoplasmosis. PASD stain.

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. Infection is usually due to inhaling contaminated air.

Pneumocystis

Pneumocystis jirovecii (or Pneumocystis carinii) can cause a form of pneumonia in people with weakened immune systems, such as premature children,patients on immunosuppressive treatment, the elderly and AIDS patients. [15]

Stachybotrys

Stachybotrys chartarum or "black mold" can cause respiratory damage and severe headaches. It frequently occurs in houses and in regions that are chronically damp. [16]

Host defense mechanisms

Endothermy

Mammalian endothermy and homeothermy are potent nonspecific defenses against most fungi. [17] 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. [18]

Barrier tissues

The skin, respiratory tract, gastrointestinal tract, and the genital-urinary tract induced inflammation[ vague ] are common bodily regions of fungal infection.

Immune response

Studies have shown that hosts with higher levels of immune response cells such as monocytes/macrophages, dendritic cells, and invariant natural killer (iNK) T-cells exhibited greater control of fungal growth and protection against systemic infection. Pattern recognition receptors (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, the cells that produce cytokine IL-17 are extremely important in maintaining innate immunity. [19]

A comprehensive comparison of distribution of opportunistic pathogens 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. [18]

See also

Related Research Articles

<i>Candida albicans</i> Species of fungus

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 usually a commensal organism, but it can become pathogenic in immunocompromised individuals under a variety of conditions. It is one of the few species of the genus Candida that cause the human infection candidiasis, which results from an overgrowth of the fungus. Candidiasis is, for example, often observed in HIV-infected patients. C. albicans is the most common fungal species isolated from biofilms either formed on (permanent) implanted medical devices or on human tissue. C. albicans, C. tropicalis, C. parapsilosis, and C. glabrata are together responsible for 50–90% of all cases of candidiasis in humans. A mortality rate of 40% has been reported for patients with systemic candidiasis due to C. albicans. By one estimate, invasive candidiasis contracted in a hospital causes 2,800 to 11,200 deaths yearly in the US. Nevertheless, these numbers may not truly reflect the true extent of damage this organism causes, given new studies indicating that C. albicans can cross the blood–brain barrier in mice.

<i>Cryptococcus neoformans</i> Species of yeast

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. In its yeast state, it is often found in bird excrement. Cryptococcus neoformans can cause disease in apparently immunocompetent, as well as immunocompromised, hosts.

<span class="mw-page-title-main">Cryptococcosis</span> Potentially fatal fungal disease

Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and brain, where it appears as a meningitis. Cough, difficulty breathing, chest pain and fever are seen when the lungs are infected. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity and confusion or changes in behavior. It can also affect other parts of the body including skin, where it may appear as several fluid-filled nodules with dead tissue.

<i>Aspergillus fumigatus</i> Species of fungus

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.

<i>Aspergillus</i> Genus of fungi

Aspergillus is a genus consisting of several hundred mould species found in various climates worldwide.

<span class="mw-page-title-main">Fungal infection</span> Disease caused by fungi to animals or humans

Fungal infection, also known as mycosis, is a disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common tinea of the skin, such as tinea of the body, groin, hands, feet and beard, and yeast infections such as pityriasis versicolor. Subcutaneous types include eumycetoma and chromoblastomycosis, which generally affect tissues in and beneath the skin. Systemic fungal infections are more serious and include cryptococcosis, histoplasmosis, pneumocystis pneumonia, aspergillosis and mucormycosis. Signs and symptoms range widely. There is usually a rash with superficial infection. Fungal infection within the skin or under the skin may present with a lump and skin changes. Pneumonia-like symptoms or meningitis may occur with a deeper or systemic infection.

<span class="mw-page-title-main">Opportunistic infection</span> Infection caused by pathogens that take advantage of an opportunity not normally available

An opportunistic infection is an infection caused by pathogens that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune system, an altered microbiome, or breached integumentary barriers. Many of these pathogens do not necessarily cause disease in a healthy host that has a non-compromised immune system, and can, in some cases, act as commensals until the balance of the immune system is disrupted. Opportunistic infections can also be attributed to pathogens which cause mild illness in healthy individuals but lead to more serious illness when given the opportunity to take advantage of an immunocompromised host.

<span class="mw-page-title-main">Gliotoxin</span> Chemical compound

Gliotoxin is a sulfur-containing mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by several species of fungi, especially those of marine origin. It is the most prominent member of the epipolythiopiperazines, a large class of natural products featuring a diketopiperazine with di- or polysulfide linkage. These highly bioactive compounds have been the subject of numerous studies aimed at new therapeutics. Gliotoxin was originally isolated from Gliocladium fimbriatum, and was named accordingly. It is an epipolythiodioxopiperazine metabolite that is one of the most abundantly produced metabolites in human invasive Aspergillosis (IA).

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.

<i>Aspergillus terreus</i> Species of fungus

Aspergillus terreus, also known as Aspergillus terrestris, is a fungus (mold) found worldwide in soil. Although thought to be strictly asexual until recently, A. terreus is now known to be capable of sexual reproduction. This saprotrophic fungus is prevalent in warmer climates such as tropical and subtropical regions. Aside from being located in soil, A. terreus has also been found in habitats such as decomposing vegetation and dust. A. terreus is commonly used in industry to produce important organic acids, such as itaconic acid and cis-aconitic acid, as well as enzymes, like xylanase. It was also the initial source for the drug mevinolin (lovastatin), a drug for lowering serum cholesterol.

<span class="mw-page-title-main">Dimorphic fungus</span> Fungi that can exist as mold or yeast

Dimorphic fungi are fungi that can exist in the form of both mold and yeast. This is usually brought about by change in temperature and the fungi are also described as thermally dimorphic fungi. An example is Talaromyces marneffei, a human pathogen that grows as a mold at room temperature, and as a yeast at human body temperature.

<i>Pseudallescheria boydii</i> Species of fungus

Pseudallescheria boydii is a species of fungus classified in the Ascomycota. It is associated with some forms of eumycetoma/maduromycosis and is the causative agent of pseudallescheriasis. Typically found in stagnant and polluted water, it has been implicated in the infection of immunocompromised and near-drowned pneumonia patients. Treatment of infections with P. boydii is complicated by resistance to many of the standard antifungal agents normally used to treat infections by filamentous fungi.

<span class="mw-page-title-main">Blastoconidium</span>

A blastoconidium is an asexual holoblastic conidia formed through the blowing out or budding process of a yeast cell, which is a type of asexual reproduction that results in a bud arising from a parent cell. The production of a blastoconidium can occur along a true hyphae, pseudohyphae, or a singular yeast cell. The word "conidia" comes from the Greek word konis and eidos, konis meaning dust and eidos meaning like. The term "bud" comes from the Greek word blastos, which means bud. Yeasts such as Candida albicans and Cryptococcus neoformans produce these budded cells known as blastoconidia.

<span class="mw-page-title-main">Fungal meningitis</span> Meningitis caused by a fungal infection

Fungal meningitis refers to meningitis caused by a fungal infection.

In biology, a pathogen, in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

Vomocytosis is the cellular process by phagocytes expel live organisms that they have engulfed without destroying the organism. Vomocytosis is one of many methods used by cells to expel internal materials into their external environment, yet it is distinct in that both the engulfed organism and host cell remain undamaged by expulsion. As engulfed organisms are released without being destroyed, vomocytosis has been hypothesized to be utilized by pathogens as an escape mechanism from the immune system. The exact mechanisms, as well as the repertoire of cells that utilize this mechanism, are currently unknown, yet interest in this unique cellular process is driving continued research with the hopes of elucidating these unknowns.

<span class="mw-page-title-main">Arturo Casadevall</span> Cuban-American scientist

Arturo Casadevall is a Bloomberg Distinguished Professor of Molecular Microbiology & Immunology and Infectious Diseases at the Johns Hopkins Bloomberg School of Public Health and Johns Hopkins School of Medicine, and the Alfred and Jill Sommer Professor and Chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. He is an internationally recognized expert in infectious disease research, with a focus on fungal and bacterial pathogenesis and basic immunology of antibody structure-function. He was elected a member of the National Academy of Sciences in 2022.

Edouard Drouhet was a physician, biologist, and medical mycologist who played a key role in understanding how anti-fungal agents such as ketoconazole and amphotericin-B can be used as therapeutic treatments in humans with superficial or deep-seated mycoses.

<span class="mw-page-title-main">CLEC6A</span> Protein-coding gene in humans

Dectin-2 or C-type lectin domain containing 6A is a protein that in humans is encoded by the CLEC6A gene. Dectin-2 is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded protein is a type II transmembrane protein with an extracellular carbohydrate recognition domain. It functions as a pattern recognition receptor recognizing α-mannans and as such plays an important role in innate immune response to fungi. Expression is found on macrophages and dendritic cells. It can also be found at low levels in Langerhans cells and peripheral blood monocytes, where expression levels could be increased upon induction of inflammation.

References

  1. 1 2 3 San-Blas G; Calderone RA, eds. (2008). Pathogenic Fungi: Insights in Molecular Biology. Caister Academic Press. ISBN   978-1-904455-32-5.
  2. ↑ "Stop neglecting fungi". Nature Microbiology. 2 (8): 17120. 25 July 2017. doi: 10.1038/nmicrobiol.2017.120 . PMID   28741610.
  3. 1 2 Geddes, Linda (10 February 2023). "'A growing threat to human health': we are ill-equipped for the dangers of fungal infections". The Guardian.
  4. 1 2 WHO fungal priority pathogens list to guide research, development and public health action. World Health Organization. 2022. ISBN   978-92-4-006025-8.
  5. ↑ English, Mary P. (1980). Medical Mycology. London: Edward Arnold Publishers Limited. p. 5. ISBN   0-7131-2795-3.
  6. ↑ Turner, S. A.; Butler, G. (2014-09-01). "The Candida Pathogenic Species Complex". Cold Spring Harbor Perspectives in Medicine. 4 (9): a019778. doi:10.1101/cshperspect.a019778. ISSN   2157-1422. PMC   4143104 . PMID   25183855.
  7. ↑ Martins N, Ferreira IC, Barros L, Silva S, Henriques M (2014). "Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment". Mycopathologia. 177 (5–6): 223–40. doi:10.1007/s11046-014-9749-1. hdl: 1822/31482 . PMID   24789109. S2CID   795450.
  8. ↑ Bennett RJ (2015). "The parasexual lifestyle of Candida albicans". Curr. Opin. Microbiol. 28: 10–7. doi:10.1016/j.mib.2015.06.017. PMC   4688137 . PMID   26210747.
  9. ↑ Beneke, E. S. (1966). Medical Mycology: Laboratory Manual (2nd ed.). Minneapolis, MN: Burgess Publishing Company. p. 161.
  10. ↑ O'Gorman CM, Fuller H, Dyer PS (2009). "Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus". Nature. 457 (7228): 471–4. Bibcode:2009Natur.457..471O. doi:10.1038/nature07528. PMID   19043401. S2CID   4371721.
  11. 1 2 3 Fan W, Kraus PR, Boily MJ, Heitman J (2005). "Cryptococcus neoformans gene expression during murine macrophage infection". Eukaryotic Cell. 4 (8): 1420–33. doi:10.1128/EC.4.8.1420-1433.2005. PMC   1214536 . PMID   16087747.
  12. ↑ Alspaugh JA, Granger DL (1991). "Inhibition of Cryptococcus neoformans replication by nitrogen oxides supports the role of these molecules as effectors of macrophage-mediated cytostasis". Infect. Immun. 59 (7): 2291–6. doi:10.1128/IAI.59.7.2291-2296.1991. PMC   258009 . PMID   2050398.
  13. 1 2 Lin X, Hull CM, Heitman J (2005). "Sexual reproduction between partners of the same mating type in Cryptococcus neoformans". Nature. 434 (7036): 1017–21. Bibcode:2005Natur.434.1017L. doi:10.1038/nature03448. PMID   15846346. S2CID   52857557.
  14. ↑ Bernstein H, Bernstein C, Michod RE (2018). "Sex in microbial pathogens". Infection, Genetics and Evolution. 57: 8–25. doi: 10.1016/j.meegid.2017.10.024 . PMID   29111273.
  15. ↑ Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN   978-0-8385-8529-0.
  16. ↑ Bitnun, Ari; Nosal, Robert M (1999). "Stachybotrys chartarum (atra) contamination of the indoor environment: Health implications". Paediatrics & Child Health. 4 (2): 125–129. doi:10.1093/pch/4.2.125. ISSN   1205-7088. PMC   2828207 . PMID   20212975.
  17. ↑ Robert, V. A.; Casadevall, A. (2009). "Vertebrate Endothermy Restricts Most Fungi as Potential Pathogens". The Journal of Infectious Diseases. 200 (10): 1623–1626. doi: 10.1086/644642 . PMID   19827944.
  18. 1 2 Gostinčar, Cene; Zajc, Janja; Lenassi, Metka; Plemenitaš, Ana; de Hoog, Sybren; Al-Hatmi, Abdullah M. S.; Gunde-Cimerman, Nina (2018-11-01). "Fungi between extremotolerance and opportunistic pathogenicity on humans". Fungal Diversity. 93 (1): 195–213. doi: 10.1007/s13225-018-0414-8 . ISSN   1878-9129.
  19. ↑ Brown GD, Drummond RA, Gaffen SL, Hise AG (2015). "Innate Defense against Fungal Pathogens". Cold Spring Harb Perspect Med. 5 (6): a019620. doi: 10.1101/cshperspect.a019620 . PMC   4426252 . PMID   25384766.

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