See also mycology
Introduction:
Fungi are nonmotile eukaryotes. They secrete exoenzymes into the environment, then absorb the digested nutrients. Most are saprophytes that decompose dead organic matter, but some are parasites of plants, animals, or humans. Fungi includes mushrooms and puffballs. In medical microbiology, one is most concerned with yeasts and molds. Although the majority of fungi are either unicellulr or colonia (they form colonies), a few complex forms such as muschrooms and puffballs are multicellular.
Cells of the microscopic fungi exist as either yeast or hyphae. A yeast cell is distinguished by its round to oval shape and mode of asexual reproduction. It grows swellings on its surface called buds which then become separate cells. Hypahe are long, threadlinke cells found in the bodies of fungi of the filamentous type. They are called molds. Fungal cells, such as Candida albicans, switch from yeast to hyphae in response to environmental cues like increased temperature, serum, neutral pH, and N-acetylglucosamine (GlcNAc). These signals activate signaling pathways, primarily the cAMP-PKA pathway, which ultimately change gene expression to promote filament growth. Physical contact with host cells, nutrient availability, and host cell presence also trigger this dimorphic transition, which is crucial for infection and invasion.
Fungi, along with bacteria, are the principal decomposers in the biosphere. They break down organic materials and return the substances locked in those molecules to circulation in the ecosystem. Fungi can break down cellulose and lingin; lingin is an insoluble organic compound that is a major constituent of wood. By breaking down such substances, fungi release carbon, nitrogen, and phosphorus from living or dead organisms and make them available to other organisms.
The term for a fungal infection is mycosis.
Fungal infections kill more than 1.6 million people yearly, according to Global Action for Fungal Infections, a research and fundraising organization. Fungal infections are estimated to kill at least 1.6 million people yearly, according to Global Action for Fungal Infections, a research and fundraising organization. In the U.S., more than 75,000 people are hospitalized with fungal infections every year, the Centers for Disease Control and Prevention said.
WHO has said that some 19 species on the list merit urgent attention from public-health officials and drug developers. Four species were designated as threats of the highest priority: Aspergillus fumigatus, a mold found abundantly in nature; Candida albicans, which is commonly found in the human body; Candida auris, a highly deadly yeast; and Cryptococcus neoformans, a fungus that can cause deadly brain infections.
Fungi are adapting to rising temperatures in ways that may make them better suited to thrive in the human body, researchers said. And more people undergoing treatments that weaken their immune systems means a larger population vulnerable to severe fungal infections.
Structure/Life Cycle/Reproduction:
Fungi are eukaryotes with a cell membrane that has ergosterol as a key component rather than cholesterol. This is an importance difference since many antifungal agents are directed towards ergosterol. Fungi also have a rigid cell wall that contains chitin as well as hyphae which are branching, threadlike tubular filaments.
Fungi have many complex reproductive strategies. Most can propagate by simple outward growth of existing hyphae or by fragmentation, in which a separated piece of mycelium can generate a whole new colony. The primary reproductive mode of fungi involves the production of various types of spores (not to be confused with the more resistant, nonreproductive bacterial endospores). Spores help the fungus disperse throughout the environment. Asexual spores are the products of mitotic division of a single parent cell, and sexual spores are formed by the fusing of two parental nucleic followed by meiosis. The majority of fungi produce sexual spores at some point. The details vary greatly. It could be as simple as the fusion of fertile hyphae of two different strains, or as complicated as a complex union of differentiated male and female structures or the development of special fruiting structures. The cap of a mushroom is actually a fruiting body designed to protect and help disseminate its sexual spores.
Detection
Fungi can be detected by 1) microscopic examination with the use of fungal stains (ex.India ink) or with KOH which dissolves host tissue leaving alkali resistant fungi or by the unique morphology of fungi (e.g., hyphae), 2) culture (media that inhibits bacterial growth like Sabouraud’s agar), 3) DNA probes or 4) serology (detection of specific antibodies).
Microsatellites, also known as short tandem repeat (STR) units: are widely used as a fast, highly sensitive, and cost effective typing technique to inbestigate the molecular diversity within fungal populations during nosocomial outbreaks,a nd for monitoring pathogens over time. Microsatellite based typing has been recognized as the optimal tool for population studies and outbreak investigations in healthcare settings, particularly for Candida auris, C. parapsilosis, Aspergillus fumigatus and Cryptococcus spp. (Hagen, “Detection of multiple nosocomial Trichosporon asahii transmission events via microsatellite typing assay, South America”, Emerging Infectious Diseases (September 2025)
Classification and disease mechanisms: (see outline)
Affecting the Nervous System
Cryptococcus neoformans: (see outlined)
Coccidioides species (Valley Fever): This fungus causes a condition that is often called “Valley Fever” in the U.S. Southwest. The morphology of Coccidioides is very distinctive. At 25C, it forms a most white to brown colony with abundant branching, septate hypae. These hyphae fragment into thick-walled blocklike arthroconidia (arthrospores) at maturity. This is a true systemic fungal infection of high virulence, as opposed to an opportunistic infection. It usually beings with pulmonary infection but can disseminate quickly throught the body. Coccidioidomycosis of the meniges is the most serious manifestation.
There are two species that casue this disease, found in different areas. C. immitis casues disease in California and C. posadasil in northern Mexico, Central and South America adn the American Southwest, especially Arizona. Sixty percent of all infections occur in Arizona. The highest incidence of coccidioidomycosis is estiamted at 100k cases per year.
Infection occurs through the inhalation of arthroconidia from two species of Coccidioides: Coccidioides immitis and C. posadasii, which are both endemic to arid and semi– arid regions of North America. The zones most affected by this mycosis are endemic regions of the southwestern United States of America (USA), northern Mexico, Central America and some regions of South America
Most people who breathe in the spores don’t get sick, but some people do. Usually, people who get sick with Valley fever will get better on their own within weeks to months, but some people will need antifungal medication.
See CDC
Fonsecaea spp.:
–F. monophora is known to infect the CNS and cause fungal brain abscess. Definitive identificaion is by molecular methods. Targeting hte ITS region of 18s rDNA, the unviersal fungal barcode, is usually sufficient. (Xess “Molecular identificaiton of Fonsecaea monophora, Novel agent of fungal brain abscess” Emerging Infectious Diseases, 30(6), June 2024).
(Xess “Molecular identificaiton of Fonsecaea monophora, Novel agent of fungal brain abscess” Emerging Infectious Diseases, 30(6), June 2024) disclosea a 3 year old pIndian patient experiencing headaches and seizures diagnosed with a fungal infection, initially misidentified as Cladophialophora bantiana. Follow up sequencing identified the isolate to be Fonsecaea monophora fungus. Contrast enhanced omputed tomography of chest and abdomen relevaed well defined nodules int he right lung and boht lobes of the liver. Cerebrospinal fluid examination showed a glucose level of 51 mg/dL (references range 40-70 mg/dL), protein level of 82 mg/dL (reference range 1-2-60 mg/dL) and leukocyte count of 45 cells/mm3 (reference range 0-20 cells/mm3) with 22% neutrophils. Persistent eosinophilia (up to 31%) was found.
–F. pedrosoi fungus: has been shown to cause brain abscesses.
Non-Aspergillus filamentous fungi:
Scedosporium spp. and Lomentospora prolificans: are non-Asperigillus filamentous fungi causing increasingly recognized invasive fungal disease (IFD) in both immunocompromised and immunocompetent patients. Scedosporium sppl includes S. apiospermum complex species, which includes S. apiospermum sensu stricto and S. boydii; L. proificans was previously known as S. prolifcans. In immunocompetent patients, localized infections have been described, such as mycetomas, osteoarticular infections, or central nervous system (CNS) infections after near-drowings. In immunocompromised hosts, scedosporiosis and lomentosporiosis mainy affect the lungs and CNS or are disseminated. Scedosporium spp. and L. prolificans can also cuase non-CNS vascular infections. Solid organ transplant was the main host risk factor. The ability of molds to invade vessels is known; angioinvasion is a kety pathogenic characteristic of invasive asperillosis and mucormycosis as well. (Bronnimann, “Deciphering unexpected vascular locaitons of Scedosporium spp. and Lomentospora prolificans fungal infections, France” Emerging infectios Diseases, 30(6), 2024).
Affecting the Respiratory System
Coccidioidomycosis, histoplasmosis, and blastomycosis are underdiagnosed fungal diseases that often mimic bacterial or viral pneumonia and can cause disseminated disease and death. These diseases are caused by inhalation of fungal spores that have distinct geographic niches in the environment (e.g., soil or dust), and distribution is highly susceptible to climate changes such as expanding arid regions for coccidioidomycosis, the northward expansion of histoplasmosis, and areas like New York reporting cases of blastomycosis previously thought to be nonendemic. The national incidence of coccidioidomycosis, histoplasmosis, and blastomycosis is poorly characterized. CDC uses the National Notifiable Diseases Surveillance System (NNDSS) to track coccidioidomycosis and histoplasmosis from states where the diseases are reportable by mandate and from those where cases are reported voluntarily. Reportable fungal diseases are designated by the state or jurisdiction and require health care professionals and laboratories to notify public health departments of cases. Coccidioidomycosis, histoplasmosis, and blastomycosis cause substantial illness in the United States, particularly coccidioidomycosis in terms of the number of cases reported (20,061). Although substantially fewer histoplasmosis and blastomycosis cases were reported, surveillance for these two diseases occurred in fewer states than for coccidioidomycosis. Even in states where histoplasmosis and blastomycosis are reportable, missed cases are likely because milder illnesses might be less commonly detected than mild coccidioidomycosis, in part because of the broader and less concentrated geographic distributions of histoplasmosis and blastomycosis than of coccidioidomycosis (37,38). In 2019, a total of 249 histoplasmosis and 147 blastomycosis cases resulted in hospitalization. Coccidioidomycosis, histoplasmosis, and blastomycosis are frequently misdiagnosed as community-acquired pneumonia or other acute lower respiratory tract infections. Misdiagnoses can lead to inappropriate therapy with antibacterial medications and delayed antifungal treatment. See CDC
Invasive pulmonary-aspergillosis (IPA): has been increasingly reported as a serious and potentially lethan complicaiton in pateints who require ICU treatment for severe influenza or COVID 19 assocaited acute respiratory failure. During the COVID-19 pandemic and pervious epidemic waves of influenza, secondary pulmonary mold infections and especially aspergillosis gained increasing attention. Alhtough exact ICU admission rates and treatment characteristics (e.g., mechnicial ventiliation, hemodynamic shock) in the context of HFRS are lacking, hantaviruses ahve also been shown to cause direct damage to the airway epithelium, potentially enablig aspergillus to invade tissue. Krause, “Invasive Pulmonary Asperillosis in Critically Ill Patients with Hantavirus Infection, Austria” Emerging Infectious Diseases, 39)6), June 2024).
Blastomycosis:
Coccidioidomycosis (Valley Fever): is caused by a fungus that lives in dust and soild, particularly in the SW United States. Symptoms include headaches, night sweats, muscle and joint pain. Coccidioidomycosis, commonly known as Valley fever, has been increasingly reported across North, South, and Central America, pointing to its reemergence as a public health concern.
Coccidioidomycosis is caused by 2 ascomycetous fungal species belonging to the genus Coccidioides: C. immitis and C. posadasii. C. immitis is primarily found in California, USA, whereas C. posadasii prevails in southern Arizona, New Mexico, and Texas, USA; parts of Central and South America. Human Coccidioides infection occurs primarily through inhalation of airborne arthroconidia produced during the saprophytic phase. Spores easily disperse by wind and can remain viable for long periods in arid environments. Once inhaled, arthroconidia transform into parasitic spherules that, upon maturation, release endospores, which can remain in the lungs or disseminate systemically. See CDC
Choanephora infundibulifera: can cause rhinosinusitis, aprticular in immunocompromised patients. Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024).
Histoplasmosis: See classification for in depth discussion
Histoplasmosis is caused by a fungus that thrives in bird and bat droppings. It affects the lungs and respirtary tract. In the United States, an estimated 60% to 90% of people who live in areas surrounding the Ohio and Mississippi River valleys. See CDC. See Dr.Fungus
Mucoymocetes: are fungi commonly found in soil or decaying matter. The fungal conidia may be inhaled form the air or introduced by skin trauma. Most humans are not affected by these spores, but those with impaired immune systomes are a great host for the fungus. In inhaled mucormycosis, hyphae invade the tissues and blood vessels of the sinuses, lungs, eyes and face. The infection is treated with intravenous antifungal medications. The fungus spreads rapdily, often requring extensive repeated surgeries to restore affected facial bones and tissues. If not aggressively treated, the fungal infection may spread into the brain and is frequently fatal.
Mucormycosis (the disease) refers to infections caused by members of the order Mucorales. While most human infections are caused by Rhizopus, Mucor and Rhizomucor, other clinically relevant organisms within the order Mucorales include: Actinomucor, Apophysomyces, Cunninghamella, Lichtheimia (previously named Absidia), Saksenaea, and Syncephalastrum
Individuals with mucormycosis can have diverse clinical manifestations contingent on the immune status of the host, the extent of the infection, and the involved organs. The most common and distinct presentation is rhino-orbital-cerebral infection, which typically occurs when fungal spores are inhaled into the sinuses. From there, the infection can remain localized, with symptoms consistent with acute sinusitis along with fever, headache, sinus pain, and nasal congestion. In vulnerable hosts however, progression of the infection with invasion of the orbit and palate and further extension to the brain may occur. This can result in a number of significant clinical abnormalities including vision loss, cranial nerve palsies, and changes in mental status. Mucormycosis can also present with pulmonary infection after spore inhalation. This is more common among patients with neutropenia due to hematologic malignancies or recipients of hematopoietic stem cell or solid organ transplants.
Early diagnosis of mucormycosis is key to rapid and appropriate treatment and improved outcomes. The diagnosis of mucormycosis requires demonstration of characteristic wide, ribbon-like, non-septate hyphae invading tissues on histopathology, accompanied with culture growth from specimens of involved sites.
Amphotericin B (AmB) is the most active drug in vitro against Mucorales and is considered the drug of choice for initial therapy. Amphotericin B belongs to a class of drugs called polyenes. It works by disrupting the cell membrane of fungal cells. Among the azole class of antifungals, posaconazole and isavuconazole are the most active agents against Mucorales and are used for stepdown therapy after response has been achieved with AmB. Posaconazole and isavuconazole are also used as salvage therapy in patients that cannot be treated with AmB.
Pneumocystis Pneumonia (PCP) is considered one the most frequent opportunistic infections in patients with AIDS. However, this fungal infection does not limit itself to this patient population. The majority of the patients who get PCP have a weakened immune system which includes: cancer patients, people taking corticosteroids for long term (e.g. for chronic lung diseases), transplant patients, and patients with inflammatory/autoimmune diseases. PCP is a serious infection that is brought by the fungus Pneumocystis jirovecii. It is spread through the air or droplet contact. Healthy adults can carry the Pneumocystis fungus in their lungs and have no symptoms, and it can spread to other people, including those with weakened immune systems. See CDC
Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in Pneumocystis jirovecii pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders.
The Pneumocystis carinii organism was first identified by Chagas in 1909, who mistook it for Trypanosoma cruzi. Initially considered to be a protozoan, P. carinii was recategorized as a fungus, based on genomic evidence. Pneumocystis jirovecii is a unicellular, obligate fungus that has two morphological forms: the cyst, a thick-walled spherical or ovoid structure; and the trophozoite, a thin-walled excysted sporozoite. JP organisms enter the alveoli through the respiratory passages. They adhere to type 1 pneumocytes, causing diffuse alveolar damage by eroding the pneumocytes. Normally, the host immune response eradicates the fungus, particularly by the action of alveolar macrophages. In immunocompromised patients; however, a decline in CD4 T-lymphocytes is associated with a CD8 T cell mediated immune response, which causes tissue damage and impairs gaseous exchange without eliminating the fungus. See Ibrahim
Affecting Gastrointestinal Tract:
Microsporidia infecting humans are still little known.
–Enterocytozoon bieneusi, by far the most frequent microsporidia species causing diseases in humans, is responsible for intestinal illness in both non- and immunocompromised patients. This species presents an astonishing genetic diversity with more than 500 genotypes described, some of which have a strong zoonotic potential. E. bieneusi infects a broad array of hosts, from wild to domestic animals.
Upon ingestion by the appropriate host, E. bieneusi invades the host cells. Enterocytes are the main cells targeted by E. bieneusi, but epithelial cells of the hepatobiliary tract can also be infected.
Affecting the Eye:
Fungi represent a very important cause of microbial eye infections, and, in some regions, especially in tropical and developing countries, they are among the main causes of blindness, causing sight-threating infections such as keratitis (infection of the cornea that can lead to corneal scarring ad loss of corneal transparency) and endophthalmitis (infection of the internal eye that usually quickly led to irreversible blindness).
Candida spp. are the most common fungi isolated in healthy individuals, but a lowering
of the eyes’ defense mechanisms could cause severe infections.
Purpureocillium Ilacinum Keratitis: In December 2024, a clinical lab notified the NYC Health Department of three patients with fungal keratitis caused by an unidnetified mold following laser eye surgery at an ophtalmology clinicl. All three patients experienced vision loss, and one required corneal transplantation. Corneal cultures from two of the patients grew Purpureocillium lilacinum, an environmental mold taht can cause a range of infections in humans; eye infections have been reported. After identificaiotn of the fungal infection, the ill patietns were started on topical voriconazole and antamycin. Eventually, all were transitioned to oral posaconazole. (MMWR, February 12, 2026, “Purpureocillium lilacinum Keratitis outbreak assocaited with an ophthalmology clinic -New York City, 2024”, 75(5)).
Affecting Wildlife:
Fungal pathogens have been implicated in wildlife population declines, posing a substantial challenge to the conservation of many species. In reptiles, most fungal pathogens are with the genera Namnizziopsis, Paranamnizziopsis and Ophidiomyces, members of the order onygenales. Of thsoe general, the most well documeted genus in wild reptiles is Ophidiomyces, consisting of the single species O. ophidiicola, which is respnosible for ophidiomycosis, also called sanke fungal disease. (Blanvillain, “Paranannizziopsis spp infection in wild vipers, Europe” Emerging Infectious Diseases, 30(5), May 2024).
Parannizziopsis spp.
Blanvillain, (“Paranannizziopsis spp infection in wild vipers, Europe” Emerging Infectious Diseases, 30(5), May 2024) rope. They swabbed the ventral and dosal areas of the snakes in duplicae using a premoistened, sterile polyester-tipped applicator from Puritan, sotred frozen swab samples at -020C, extracted DNA from the samples uing PrepMan Ultra Sample preparation Reagent rom ThermoFisher as well as Qiagen blood and Tissue Kit. disclsoes describe the detection of Parannizziopsis sp. fungas in a wild population of vipers in Europe.
Affecting Plants (and sometimes mammals):
Mucorales Group: consists of over 260 sepcies in 55 genera that are ubiquitous in wet, organic evenironments, About 40 species are clincially isgnificant, cuasing invasive infection (mcormycosis) cheifly in persons with diabets and immuno-compromising conditions.
–Genus Choanephora (family Choanephoracae): contains 2 species, C. infundibulifera and C. cucurbitarum. These species are saprophtes or parasites of plants that can promote spoilage and disease. C. cucrbitarum, the more commonly recognized species, causes wet blight, flower rot blight, and leaft blight, chiefly on summer squash and other cucurbits.
The optimal treatment for infections caused by Choanephora speies is unkown. The minimal inhibitory conentraiton correlation with treamtnet response in vivo is unkown, but he in vitro antifungal minimal inhibitory conentrations against this isolate suggest amphoteric B might ahve greater activity than posaconazole and isavuconazole, which are used to treat mucormycosis caused by other species. Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024).
—-C. infundibulifera: infrequently causes plant disease but has been implicated in twig and leaf rot and blossom blight. On potato-carot or potato dexrose agar, colonies grow rapidly at 25C with abundant white, pale-yellow, or brown mycelia and sporangiophores, with sporangia arising from substrate mycelium or nonsepttate, unbrached, hyaline aerial hyphae. Definitive identificaiton is based on morphology and sequencing of the nuclear ribosomal internal transcribed spacer region and the D1 nad D2 domains on the 28S rRNA gene. (Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024).
Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024) disloses an 18 year old man with systemic symptoms and lymphadenopathy who received a diagnosis of ealry T cell precursor acute lymphoblastic leukemia. Induction chemotherpay was complicated by rhinosinusitis linked to speies of Alternaria and Curvularia and presumed funal pneumonia. The treatment consisted of debridement of his nasal and sinus passages and advinistration of liposomal amphotericin B, followed by oral posaconazole for 5 monhts. Thereafter, posaconazole secondary prophylaxis was prescirbed druing severe neutrophenia. Later on computed tomography of the sinuses showed evdience of rhinosinusiti. A magnetic resonance imaging scan revealed soft tissue swelling, right nodularity and irregular nasal septal mucosal thinning, sinus mucosal thickening, and enhanced right jugular lymph nodes. Computed tomography of the chest yeilded unremarkable resutls. The patient udnerwent nasal endoscopy and debridement, hmatoxyline and iosin-stained sections from a biopsy of the right nasal septum revealed necrotic tissue with numerous hyaline fungal elements with a wide, ribbon-like appearance. Two isolates form a fungal culture showed a curvularia speies on a lactophenol cotton blue stain. Further testing by matrix-assisted laser desorption/ionization time of flight mass spectrometry (Vitek MS V3.2; bioMerieux) revealed the isolate to be Curvalaria lunata. The other isolated was determeind to be Choanephora infundibulifera by phenotypic characterization and BAST searches using the nuclear ribosomal internal transcribed spacer region and the D1 and D2 domains of the 28S rRNA gene. BLAST search reuslts matched with srtains C. infundibulifera, C. infundibulifera.
Paraconiothyrium cyclothyrioides: is an invironmental mold found on plants and in soil. Seven cases of human P. cyclothyrioides infection have been reported, most cutaneous. The incidence of P. cyclothyrioides and other are mold infection s might be underestimated, however, because routine lab methods often cannot identify them. Reliable identification usually requires molecular diagnostics that are not commonly performed. Cutaneous Paraconiothryium cyclothyrioides infection has been reported in lung transplant recipients (see (“Cutaneous Paraconiothyrium cyclothyrioides infetion in lung transplant recipitent, Georgia, USA, CDC, 32(3), 2026).
Treatment: (See outline)