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, along with bacteria, are the principal decomposers in the biosphere. They break down organic materiasl and return the substances locked in those molecuels to circulation in the ecosystem. Fungi can break down cellulose na dlignin; 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.

Structure

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.

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).

Classification and disease mechanisms: 

Fungi can cause health issues in numans by acting as allergens that trigger immune responses or by direct infection, usually of the skin or nails, or by producing toxins that are ingested.

Fungi are informally divided into unicellular yeasts and filamentous molds based on their overall appearance. Fungi are also sometimes classified as follows:

superficial mycoses which live on dead skin and hair and do not elicit an immune response. Superficial mycoses include Tinea versicolr, Tinea nigra, Black and White piedra which grow on hair shafts.

cutaneous mycoses which are caused by dermatophytes and infect keratinized skin, hair and nails. Cutaneous mycoses invoke an immune response. Diseases are very common and include ringworm or tinea (e.g., Tinea pedis).

–Dermatophytosis, (also called ringworm or tinea), is a common superficial fungal skin infection most often caused by Trichophyton, Microsporum, or Epidermophyton fungi and often treated using over-the-counter topical antifungal agents.

Tinea is a very common fungal infection of the skin. It is often called “ringworm” because the rash is circular, with a ring-like appearance.

Oral terbinafine is a first-line antifungal treatment for extensive skin infections, which typically occur in immunocompromised or older persons. Outbreaks of extensive, recalcitrant, and frequently terbinafine-resistant dermatophytosis in immunocompetent persons are ongoing in southern Asia because of the recently emerged dermatophyte Trichophyton indotineae (formerly Trichophyton mentagrophytes genotype VIII). T. indotineae typically causes tinea faciei, corporis, or cruris; easily spreads person-to-person; and has been reported globally, including in multiple US states. Laboratory identification requires advanced molecular techniques because culture-based methods cannot distinguish T. indotineae from other Trichophyton species. There is an emergence of antifungal-resistant T. indotineae as a cause of genital lesions and possible acquisition and transmission through sexual contact. Clinicians should be aware that visual inspection without diagnostic testing cannot reliably distinguish dermatophytosis from other causes of inflammatory skin conditions (e.g., contact dermatitis). Spivack “Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae”

—-Tinea pdeis (foot) causes itching, scaling, flaking and sometimes blistering of the affected areas. Tinea pedis are fungi that are typically transmitted in moist communal areas where people go barefoot, such as around swimming pools or in showers and require a warm moist environment like the inside of a shoe to incubate. Tinea cruris (groin) also known as “crotch itch” or “jock itch” is a dermatophyte fungal infection of the groin region. Tinea corporis (body) is a superficial fungal infection of the arms and legs, especially on glabrous skin. However it may occur on any part of the body. It presents as a annual, marginated plaque with thin scale and clear center. Treatment includes grisofluvine, itraconazole and clotrimazole cream.

Ketoconazole is a synthetic imidazole antifungal drug that is used to treat fungal infections such as tinea.

Subcutaneous mycoses are lesions in deeper skin layers usually caused by a trauma such as a thorn. For example, sporotrichosis (“Rose grower’s disease”) typically occurs when one is pricked by a thorn which has the Sporothrix schenckii fungus agent. Other subcutaneous infections are Chromoblastomycosis and Mycetoma.

Systemic mycoses are inheritently infectious and include (1) Histoplasmosis otherwise known as “Darling’s” “cave” or “spelunker’s” disease. Histoplasmosis occurs in the midwest. Infection is due to inhalation of conidia or hyphal fragments which are phagocytized by pulmonary macrophages. It is usually found on bird dropping and is a dimorphic fungus in that it can exist in the yeast (e.g., macophages) or mold (e.g., soil) form. Treatment may include itraconazole and/or amphotericin B. (2) Blastomycosis otherwise known as “Gilchrist’s” or “Chicago” disease is endemic in Ohio and the Mississippi Valley. Treatment can again be amphotericin B. (3) Coccidioidomycosis otherwise known as “Posada-Wernicke” or “San Joaquin Valley vever” is endemic in California and Texas. Treatment can again include amphotericin

B. opportunistic mycoses are pathogenic in immunocompetent individuals and include (1) Aspergillosis such as A. fumigatus, A. flavus, A. niger are ubiquitous in damp basements and vegetation. It can cause blockage of airways from fungal masses. Treatment can include surgery, amphotericin B or itraconazole. (2) Cryptococcosis neoformans (3) Candidiasis is a dimorphic fungus with yeast on mucosal surfaces. It is actually part of one’s normal flora in skin, mouth and intestines and stays as yeast but it forms hyphae when invasive. Treatment includes cessation of antibiotic and can also include itraconzaole.

Most fungi are not pathogens but they can produce toxins and cause allergies (primarily IgE mediated). For example, spoiled peanuts and other grains contain coumarin derivatives produced by Aspergillus flavus and cause liver damage. Claviceps purpura also infects grains and produces lysergic acid diethylamide, commonly known as “LSD”.

Medically Important Fungus

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.

Aspergillus fumigatus: which most people inhale every day, can cause disease of the lungs but can also colonize other parts of the body including the brain, infectious-disease experts said. Hospitalizations related to severe Aspergillus infectionss are increasing.

Candida albicans causes oral thrush and vaginal yeast infections, and can also infect the blood, heart and other internal organs. The mortality rate of Candida auris, which often spreads in hospitals, can be as high as 60%, according to the CDC said.

Candidad albicans is normally present on the skin of the glans and can be a considered normal flora. The yeast can cause infection in certain cicumstances, especially when the patient has underlying conditions, poor hygiene, overgrowth, or changes in basline pH. Although yest infection is the most common cause, there are several other etiologies that exist and must be considered by the provider. These include the following infectious and noninfectious etiologies:

• Candidal species (most commonly associated with diabetes)
• Group B and group A beta-hemolytic streptococci
• Neisseria gonorrhea
• Chlamydia species
• Anaerobic infection
• Human papillomavirus
• Gardnerella vaginalis
• Treponema pallidum (syphilis)
• Trichomonas species
• Borrelia vincentii and Borrelia burgdorferiNoninfectious etiologies:
  • Poor personal hygiene (most common)
  • Chemical irritants (e.g.,  spermicides, detergents, perfumed soaps and shower gels, fabric conditioners)
  • Edematous conditions, including congestive heart failure (right-sided), cirrhosis, and nephrosis
  • Drug allergies (e.g., tetracycline, sulfonamide)
  • Morbid obesity
  • Allergic reaction (condom latex, contraceptive jelly)
  • Fixed-drug eruption (sulfa, tetracycline)
  • Plasma cell infiltration (Zoon balanitis)
  • Autodigestion by activated pancreatic transplant exocrine enzymes
  • Trauma
  • Neoplastic conditions

Some fungal infections can be passed on sexually – these include Thrush, Jock Itch (like athletes foot, but around the genitals) and Balanitis (inflammation of the end of the penis). Infectious etiologies of balanitis include certain fungi like yeast and certain bacteria or viruses (including those that cause STDs such as gonorrhea).

Affecting the Nervous System

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.

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.

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: 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 decarying 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 fugaus 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.

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

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.

Treatment:

There are four classes of antifungal medicines for invasive fungal disease, and most drugs in these classes are toxic, even at low doses, infectious-disease experts say. A new class to treat severe diseases hasn’t been approved in over 20 years. Fungal infections receive less than 1.5% of all infectious-disease research funding.

Several antifungal drugs in development, including Scynexis’ ibrexafungerp and Pfizer’s fosmanogepix, have been shown in clinical trials to be effective against Aspergillus and Candida infections. Cidara Therapeutics Inc. has submitted its drug rezafungin for Food and Drug Administration approval to treat Candida infections, including severe disease; and F2G Ltd. said its antifungal olorofim had been found effective at eradicating Aspergillus and other rare molds in a Phase 2 clinical trial.