Pathogenic fungus

Pathogenic fungi are fungi that cause disease in humans or other organisms. Approximately 300 fungi are known to be pathogenic to humans.[1] The study of fungi pathogenic to humans is called "medical mycology". Although fungi are eukaryotic, many pathogenic fungi are microorganisms.[2] The study of fungi and other organisms pathogenic to plants is called plant pathology.

Candida
Candida. Pap test specimen. Pap stain.

Candida species cause infections in individuals with deficient immune systems. 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.[3] C. albicans has a parasexual cycle that appears to be stimulated by environmental stress.[4]

Aspergillus
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.[2]

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.[5] A. fumigatus has a fully functional sexual cycle that produces cleistothecia and ascospores.

Cryptococcus
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. Cryptococcus laurentii and Cryptococcus albidus 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.[2]

Infecting C. neoformans cells are usually phagocytosed by alveolar macrophages in the lung.[6] The invading C. neoformans cells may be killed by the release of oxidative and nitrosative molecules by these macrophages.[7] However some C. neoformans cells may survive within the macrophages.[6] 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.[6]

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.[8] Meiosis may facilitate repair of C. neoformans DNA in response to macrophage challenge.[8][9]

Histoplasma
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, the elderly and AIDS patients.[10]

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.

Host defense mechanisms

Endothermy

Mammalian endothermy and homeothermy are potent nonspecific defenses against most fungi.[11]

Barrier tissues

The skin, respiratory tract, gastrointestinal tract, 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 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.[12]

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See also

References
  1. "Stop neglecting fungi". Nature Microbiology. 2 (8): 17120. 25 July 2017. doi:10.1038/nmicrobiol.2017.120. PMID 28741610.
  2. San-Blas G; Calderone RA, ed. (2008). Pathogenic Fungi: Insights in Molecular Biology. Caister Academic Press. ISBN 978-1-904455-32-5.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 978-0-8385-8529-0.CS1 maint: extra text: authors list (link)
  11. 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.
  12. Brown GD, Drummond RA, Gaffen SL, Hise AG (2015). "Innate Defense against Fungal Pathogens". Cold Spring Harb Perspect Med. 5: a019620–a019620. doi:10.1101/cshperspect.a019620.

Further reading
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