Pathogenic fungus
Pathogenic fungiarefungithat cause disease in humans or otherorganisms.Although fungi areeukaryotic,many pathogenic fungi aremicroorganisms.[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 eithertuberculosisormalaria—about two million people per year.[3]
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 toplantlife than those of theanimal kingdom.[5]The study of fungi and other organisms pathogenic to plants is calledplant pathology.
Pathogens of particular concern
[edit]According to theWorld 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),Histoplasmaspp.,eumycetomacausative agents,Mucorales,Fusariumspp.,Candida tropicalis,Candida parapsilosis.
- Medium priority
- Scedosporiumspp.,Lomentospora prolificans,Coccidioidesspp.,Pichia kudriavzeveii(Candida krusei),Cryptococcus gattii,Talaromyces marneffei,Pneumocystis jirovecii,Paracoccidioidesspp.
Candida
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/3/34/Candida_pap_1.jpg/220px-Candida_pap_1.jpg)
Candidaspecies 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-typecell-mediated immunity(CMI) is required for clearance of a fungal infection. Candida albicansis a kind of diploidyeastthat commonly occurs among the humangut microflora.C. albicansis anopportunistic pathogenin humans. Abnormal over-growth of this fungus can occur, particularly inimmunocompromisedindividuals.[7]C. albicanshas aparasexual cyclethat 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 ofCandidamay be pathogenic as well, includingCandida stellatoidea,C. tropicalis,C. pseudotropicalis,C. krusei,C. parapsilosis,andC. guilliermondii.[9]
Aspergillus
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/c/cd/Pulmonary_aspergillosis.jpg/220px-Pulmonary_aspergillosis.jpg)
The most common pathogenic species areAspergillus fumigatusandAspergillus flavus.Aspergillus flavus producesaflatoxinwhich is both a toxin and acarcinogenand which can potentially contaminate foods such as nuts.Aspergillus fumigatusandAspergillus clavatuscan causeallergicdisease. SomeAspergillusspecies cause disease on grain crops, especiallymaize,and synthesizemycotoxinsincludingaflatoxin.Aspergillosisis the group of diseases caused byAspergillus.The symptoms include fever, cough, chest pain or breathlessness. Usually, only patients with weakenedimmune systemsor with otherlungconditions are susceptible.[1]
The spores ofAspergillus fumigatusare ubiquitous in the atmosphere.A. fumigatusis an opportunistic pathogen. It can cause potentially lethal invasive infection in immunocompromised individuals.[10]A. fumigatushas a fully functional sexual cycle that produces cleistothecia andascospores.[citation needed]
Cryptococcus
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/3/36/Cryptococcus.jpg/220px-Cryptococcus.jpg)
Cryptococcus neoformanscan cause a severe form ofmeningitisand meningo-encephalitis in patients withHIVinfection andAIDS.The majority ofCryptococcusspecies live in the soil and do not cause disease in humans.Cryptococcus neoformansis the major human and animal pathogen.Papiliotrema laurentiiandNaganishia albida,both formerly referred toCryptococcus,have been known to occasionally cause moderate-to-severe disease in human patients with compromised immunity.Cryptococcus gattiiis endemic to tropical parts of the continent of Africa and Australia and can cause disease in non-immunocompromised people.[1]
InfectingC. neoformanscells are usually phagocytosed byalveolar macrophagesin the lung.[11]The invadingC. neoformanscells may be killed by the release of oxidative and nitrosative molecules by these macrophages.[12]However someC. neoformanscells 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 toantifungalagents. In order to survive in the hostile intracellular environment of the macrophage, one of the responses ofC. neoformansis toupregulategenesemployed in responses tooxidative stress.[11]
The haploid nuclei ofC. neoformanscan undergo nuclear fusion (karyogamy) to become diploid. These diploid nuclei may then undergomeiosis,includingrecombination,resulting in the formation of haploidbasidiosporesthat are able to disperse.[13]Meiosis may facilitaterepairofC. neoformansDNA in response to macrophage challenge.[13][14]
Histoplasma
[edit]![](https://upload.wikimedia.org/wikipedia/commons/thumb/3/36/Histoplasma_pas-d.jpg/220px-Histoplasma_pas-d.jpg)
Histoplasma capsulatumcan causehistoplasmosisin humans, dogs and cats. The fungus is most prevalent in the Americas, India and southeastern Asia. It is endemic in certain areas of theUnited States.Infection is usually due to inhaling contaminated air.
Pneumocystis
[edit]Pneumocystis jirovecii(or Pneumocystis carinii) can cause a form ofpneumoniain people with weakenedimmune systems,such as premature children, patients on immunosuppressive treatment, the elderly andAIDSpatients.[15]
Stachybotrys
[edit]Stachybotrys chartarumor "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
[edit]Endothermy
[edit]Mammalianendothermyand 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
[edit]Theskin,respiratory tract,gastrointestinal tract,and thegenital-urinary tractinduced inflammation[vague]are common bodily regions of fungal infection.
Immune response
[edit]Studies have shown that hosts with higher levels ofimmune response cellssuch asmonocytes/macrophages,dendritic cells,andinvariant natural killer (iNK) T-cellsexhibited 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 mucosalcandidiasis,the cells that producecytokine IL-17are extremely important in maintaininginnate immunity.[19]
Link to extremotolerance
[edit]A comprehensive comparison of distribution ofopportunistic pathogensand stress-tolerant fungi in the fungal tree of life showed thatpolyextremotoleranceand opportunistic pathogenicity consistently appear in the same fungal orders and that the co-occurrence of opportunism andextremotolerance(e.g.osmotoleranceandpsychrotolerance) is statistically significant. This suggests that some adaptations to stressful environments may also promote fungal survival during the infection.[18]
See also
[edit]- List of human diseases associated with infectious pathogens
- Microbiology
- Microsporidia
- Mycology
- Plant pathology
- Plague Inc.
References
[edit]- ^abcSan-Blas G; Calderone RA, eds. (2008).Pathogenic Fungi: Insights in Molecular Biology.Caister Academic Press.ISBN978-1-904455-32-5.
- ^"Stop neglecting fungi".Nature Microbiology.2(8): 17120. 25 July 2017.doi:10.1038/nmicrobiol.2017.120.PMID28741610.
- ^abGeddes, Linda (10 February 2023)."'A growing threat to human health': we are ill-equipped for the dangers of fungal infections ".The Guardian.
- ^abWHO fungal priority pathogens list to guide research, development and public health action.World Health Organization. 2022.ISBN978-92-4-006025-8.
- ^English, Mary P.(1980).Medical Mycology.London:Edward Arnold Publishers Limited.p. 5.ISBN0-7131-2795-3.
- ^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.ISSN2157-1422.PMC4143104.PMID25183855.
- ^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.PMID24789109.S2CID795450.
- ^Bennett RJ (2015)."The parasexual lifestyle of Candida albicans".Curr. Opin. Microbiol.28:10–7.doi:10.1016/j.mib.2015.06.017.PMC4688137.PMID26210747.
- ^Beneke, E. S. (1966).Medical Mycology: Laboratory Manual(2nd ed.). Minneapolis, MN:Burgess Publishing Company.p. 161.
- ^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.PMID19043401.S2CID4371721.
- ^abcFan 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.PMC1214536.PMID16087747.
- ^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.PMC258009.PMID2050398.
- ^abLin 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.PMID15846346.S2CID52857557.
- ^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.PMID29111273.
- ^Ryan KJ; Ray CG, eds. (2004).Sherris Medical Microbiology(4th ed.). McGraw Hill.ISBN978-0-8385-8529-0.
- ^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.ISSN1205-7088.PMC2828207.PMID20212975.
- ^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.PMID19827944.
- ^abGostinčar, 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.ISSN1878-9129.
- ^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.PMC4426252.PMID25384766.
Further reading
[edit]- Almeida F, Rodrigues ML, Coelho C (2019)."The Still Underestimated Problem of Fungal Diseases Worldwide".Front Microbiol.10:214.doi:10.3389/fmicb.2019.00214.PMC6379264.PMID30809213.