What is Aspergillus? Diagnosis and prevention of aspergillosis

Aspergillus

(/ˌæsпərˈdʒɪлəs/) is a genus of several hundred mold species found in a variety of climates around the world.

Aspergillus

was first cataloged in 1729 by an Italian priest and biologist.
Pier Antonio Micheli. Examining the mushrooms under a microscope, Micheli recalled the form of aspergillus
(sprinkler of holy water), from the Latin
sparger
(to sprinkle) and named the genus accordingly.[1]
Aspergillum is an asexual common spore-forming Aspergillus
; About one-third of species also have a sexual stage.[2]Aspergillus can be removed from the home using rubbing alcohol (70%) or a strong air purifier to eliminate the effects on the lungs.

Growth and spread

Aspergillus
in detail about tomato

Aspergillus

is defined as a group of conidial fungi, that is, fungi in an asexual state.
However, some are known to have a teleomorph (sexual state) in Ascomycota. With DNA evidence, all members of the genus Aspergillus
are members of Ascomycota.

Members of the genus have the ability to grow where there is high osmotic pressure (high concentration of sugar, salt, etc.). Aspergillus

The species is highly aerobic and occurs in almost all oxygen-rich environments, where they typically grow as molds on the surface of a substrate as a result of high oxygen tension.
Fungi typically grow on carbon-rich substrates such as monosaccharides (Such as glucose) and polysaccharides (Such as amylose). Aspergillus
species are common contaminants of starchy foods (such as bread and potatoes) and grow on many plants and trees.[
citation needed
]

In addition to growing on carbon sources, many Aspergillus

demonstrate oligotrophy where they are able to grow in a nutrient-poor environment or in an environment completely lacking essential nutrients.
Aspergillus niger
is a prime example of this; it can be found on damp walls as it is the main component of mold.

Several species of Aspergillus

, including
A. niger
and
A. fumigatus
, readily colonize structures,[4] with a preference for warm and moist or damp areas such as bathrooms and around window frames.[5]

Aspergillus

millions in pillows.[6]

Causes of aspergillosis

The causative agents of aspergillosis in humans can be the following types of mold fungi of the genus Aspergillus: A. flavus, A. Niger, A. Fumigatus, A. nidulans. A. terreus, A. clavatus. Aspergillus are aerobes and heterotrophs; are able to grow at temperatures up to 50°C and can be preserved for a long time when dried and frozen. In the environment, Aspergillus is ubiquitous - in soil, air, and water. Favorable conditions for the growth and reproduction of aspergillus are found in ventilation and shower systems, air conditioners and humidifiers, old clothes and books, damp walls and ceilings, long-term stored food products, agricultural and indoor plants, etc.

Infection with aspergillosis most often occurs through inhalation when inhaling dust particles containing the mycelium of the fungus. Agricultural workers, employees of paper spinning and weaving enterprises, flour millers, and pigeon breeders are at greatest risk of developing the disease, since pigeons are more likely than other birds to suffer from aspergillosis. The occurrence of a fungal infection is facilitated by infection during invasive procedures: bronchoscopy, puncture of the paranasal sinuses, endoscopic biopsy, etc. Contact transmission of aspergillosis through damaged skin and mucous membranes cannot be ruled out. Nutritional infection is also possible through consumption of food products contaminated with Aspergillus (for example, chicken meat).

In addition to exogenous infection with Aspergillus, cases of autoinfection (by activation of fungi that live on the skin, mucous membrane of the pharynx and respiratory tract) and transplacental infection are known. Risk factors for the incidence of aspergillosis include immunodeficiencies of any origin, chronic diseases of the respiratory system (COPD, tuberculosis, bronchiectasis, bronchial asthma, etc.), diabetes mellitus, dysbacteriosis, burn injuries; taking antibiotics, corticosteroids and cytostatics, radiotherapy. There are frequent cases of the development of mycoses of mixed etiology, caused by various types of fungi - aspergillus, candida, actinomycetes.

Commercial significance

Various Penicillium
,
Aspergillus
species and other fungi growing in axenic culture Historical model
of Aspergillus
, Botanical Museum Greifswald

Aspergillus species

important from a medical and commercial point of view.
Some species can cause infection in humans and other animals. Some infections found in animals had been studied for years, while other species found in animals were described as new and specific to the disease being studied, and others were known as names already in use for organisms such as saprophytes. More than 60 Aspergillus
species are pathogens of medical relevance.[7] In humans, a number of diseases, such as outer ear infections, skin lesions and ulcers, classified as mycetomas are found.

Other species play an important role in commercial microbial fermentation. For example, alcoholic drinks such as Japanese sake

often made from rice or other starchy ingredients (such as cassava) rather than grapes or malted barley.
Typical microorganisms used to produce alcohol, such as yeasts of the genus Saccharomycetes
, cannot ferment these starches.
Consequently, Koji
molds such as
Aspergillus oryzae
are used to break down starches into simpler sugars.[8]

Representatives of the genus are also sources of natural products that can be used in the development of drugs to treat human diseases.[9]

Possibly the largest use of Aspergillus niger

is the main source of citric acid;
this organism accounts for more than 99% of global citric acid production, or more than 1.4 million tons per year.[ citation needed
]
A. niger
is also widely used to produce domestic and foreign enzymes, including glucose oxidase, lysozyme, and lactase.[10] In these cases, the crop is rarely grown on a solid substrate, although this is still common practice in Japan, but is more often grown as a submerged culture in a bioreactor. In this way, the most important parameters can be strictly controlled and maximum performance can be achieved. This process also greatly simplifies the separation of the important chemical or enzyme from the medium and is therefore much more economical.

Diagnostics

Aspergillosis in adults requires a thorough and comprehensive diagnosis, which, first of all, is necessary to identify the type and severity of such a disease.

The first stage of establishing the correct diagnosis is carried out by the clinician to whom the person contacted, based on the predominant symptom. The doctor needs:

• get acquainted with the medical history and life history of the patient - this may indicate some etiological factors;
• conduct a detailed survey of the patient to find out the first time of onset and the degree of intensity of symptom expression. This will enable the clinician to determine the severity of the disease;
• perform a thorough physical examination, which, depending on the situation, may include an ophthalmological examination of the eyes, palpation of the anterior wall of the abdominal cavity, examination of the condition of the skin and nail plates, and listening to the lungs using a phonendoscope.

Instrumental diagnosis of aspergillosis includes:

• chest x-ray;
• biopsies;
• bronchoscopy;
• spirometry;
• CT.

Laboratory tests will also vary depending on the nature of the infection. In most cases, these include:

• study of discharge from the sinuses or external auditory canal;
• microscopic examination of feces;
• general blood test - may indicate the occurrence of an allergic or inflammatory process;
• analysis of sputum produced when coughing - to identify Aspergillus particles;
• blood biochemistry;
• scraping from the skin or nail plates;
• imprint from the surface of the cornea;
• PCR.

Such activities will help not only make the correct diagnosis, but also carry out a differential diagnosis of such a disease.

Study

Four three-day-old Aspergillus
colonies.
Clockwise from top left: A. nidulans
laboratory strain;
a similar strain with a mutation in the yA marker gene is involved in green pigmentation; an A. oryzae
strain used in soybean fermentation;
A. oryzae

Aspergillus
scan taken at 235 magnification under a scanning electron microscope

A. nidulans

(
Emericella nidulans
) has been used as a research organism for many years and was used by Guido Pontecorvo to show parasexuality in mushrooms.
Recently, A. nidulans
was one of the first organisms to obtain a genome from researchers at the Broad Institute.
Since 2008, seven more Aspergillus
species have had their genomes sequenced: the industrially useful
A. niger
(two strains),
A. oryzae
, and
A. terreus
, and the pathogens
A. clavatus
,
A. fischerianus
(
Neosartorya fischeri
),
A. flavus
, and
A. fumigatus
(two strains).[11]
A. fischarianus
is almost never pathogenic, but is very closely related to the common pathogen
A. fumigatus
;
this has been partially sequenced to better understand A. fumigatus
pathogenicity.[12]

Sexual reproduction

Of the 250 Aspergillus species, about 64% have no known sexual state.[13] However, many of these species probably have an as-yet unidentified sexual stage.[13]Sexual reproduction occurs in fungi in two fundamentally different ways. These are outcrossing (in heterothallic fungi), in which two different individuals contribute the nuclei, and self-fertilization or selfing (in homothallic fungi), in which both nuclei come from the same individual. In recent years, sexual cycles have been discovered in many species previously thought to be asexual. These discoveries reflect recent experimental attention to species of particular importance to humans.

A. fumigatus

it is the most common species causing disease in immunocompromised people.
In 2009, A. fumigatus
was shown to have a heterothallic, fully functional sexual cycle.[14] Isolates of complementary mating types are necessary for sex to occur.

A. flavus

is a major producer of carcinogenic aflatoxins in crops around the world. It is also an opportunistic person and animal. pathogen, causing aspergillosis in immunocompromised individuals. In 2009, the sexual condition of this heterothallic fungus occurs when strains of opposite mating types were grown together under appropriate conditions.[15]

A. lentulus

is an opportunistic human pathogen that causes invasive aspergillosis with a high mortality rate.
In 2013, A. lentulus
was found to have a heterothallic functional sexual reproduction system.[16]

A. terreus

widely used industrially to produce important organic acids and enzymes and was the original source of a cholesterol-lowering drug.
lovastatin. In 2013, A. terreus
was found to be capable of sexual reproduction by crossing strains of opposite mating types under appropriate culture conditions.[17]

These findings from Aspergillus

species is consistent with the accumulated evidence from studies of other eukaryotic species, this sex was likely present in the common ancestor of all eukaryotes.[18][19]

A. nidulans

, a homothallic fungus, is capable of self-fertilization. Self-fertilization involves activation of the same sex-specific mating pathways in the outcrossing species, that is, self-fertilization does not bypass the required pathways for outcrossing, but instead requires activation of these pathways in one individual.[20]

Among those Aspergillus

Species that exhibit a sexual cycle are overwhelmingly homothallic (self-fertilizing) in nature.[21]
This observation suggests Aspergillus
species can usually maintain sex, although little genetic variation is produced by homothallic self-fertilization.
A. fumigatus
, a heterothallic (outcrossing) fungus that occurs in areas with widely varying climates and environments, also shows little genetic variation either within geographic regions or globally,[22] again suggesting that sex is, in this case, opposite sex, can be maintained even with little genetic variation.

Genomics

Simultaneous publication of three Aspergillus species

The genome manuscript in
Nature
in December 2005 established this genus as the leading genus of filamentous fungi for comparative genomic studies.
Like most major genome projects, this effort was the result of collaboration between a large sequencing center and a related community of scientists. For example, the Institute for Genomic Research (TIGR) has worked with the A. fumigatus
community.
A. nidulans
was sequenced at the Broad Institute.
A. oryzae
sequencing was performed in Japan at the National Institute of Advanced Industrial Science and Technology.
The Department of Energy's Joint Genome Institute has published the sequence data of the citric acid-producing strain of A. niger
.
TIGER, now renamed the J. Craig Venter Institute, currently leads the A. flavus
genome project.[23]

Aspergillus

is characterized by high levels of genetic diversity and, using protostomal divergence as a scale, is as diverse as the vertebrate phylum, although both interspecific and intraspecific genome structure are relatively plastic.[24]
The genomes of some Aspergillus
species, such as
A. flavus
and
A. oryzae
, are richer and about 20% larger than others, such as
A. nidulans
and
A. fumigatus
. Several mechanisms can explain this difference, although a combination of segmental duplication, genome duplication, and horizontal gene transfer acting piecemeal is well supported.[25]

Genome sizes for sequenced Aspergillus

range from 29.3 Mb for
A. fumigatus
to 37.1 Mb for
A. oryzae
, while the number of predicted genes ranges from approximately 9,926 for
A. fumigatus
to approximately 12,071 for
A. oryzae
.
The genome size of the enzyme-producing strain of A. niger
is intermediate in size at 33.9 Mb.[1]

Prognosis and prevention

The most favorable course is observed with aspergillosis of the skin and mucous membranes. The mortality rate from pulmonary forms of mycosis is 20-35%, and in people with immunodeficiency - up to 50%. The septic form of aspergillosis has a poor prognosis.

Measures to prevent infection with aspergillosis include measures to improve sanitary and hygienic conditions: combating dust in production, wearing personal protective equipment (respirators) by workers in mills, granaries, vegetable stores, weaving enterprises, improving ventilation of workshops and warehouses, regular mycological examination of persons from risk groups.

Pathogens

A little Aspergillus

species cause serious diseases in humans and animals.
The most common pathogenic species are A. fumigatus
and
A. flavus
, which produces aflatoxin which is both a toxin and carcinogen and can contaminate foods such as nuts.
The most common species that cause allergic diseases are A. fumigatus
and
A. clavatus
.
Other species are important as agricultural pathogens. Aspergillus
species cause disease in many grain crops, especially corn, and some variants synthesize mycotoxins, including aflatoxin.
Aspergillus
can cause neonatal infections.[26]

A. fumigatus

(most common type) infections are primary pulmonary infections and have the potential to develop into rapidly necrotizing pneumonia with the potential to spread.
The organism can be distinguished from other common mold infections based on the fact that it takes the form of mold both in the environment and in the host (unlike fungi albicans
which is a dimorphic mold in the environment and yeast in the body).

Symptoms of aspergillosis in humans

Since the respiratory system takes the first blow, the main symptoms of aspergillosis in humans begin to appear precisely from the respiratory system. In a third of cases, the fungus enters the body through the blood and lymph flow and spreads to all organs. This type of aspergillosis has a high mortality rate of about eighty percent. The rarest is cutaneous aspergillosis.

If the fungus has settled on the surface and has not penetrated the mucous membrane, as happens with tracheobronchitis or aspergilloma, then patients note the following symptoms: chronic cough with sputum, sometimes with blood during a strained cough. Most often in such cases there are pathologies of the lungs.

In response to the penetration of spores into the body, human tissues develop certain inflammatory reactions. The most common two types of inflammation are serous-desquamative and fibrous-purulent. With serous-desquamative inflammation, aspergillus causes exfoliation of the epithelium, membranes of the stomach, and lungs with the release of exudate (plasma with blood elements). In the second type - fibropurulent - aspergillus causes the release of exudate with fibrin (clotted blood protein) and a purulent component. The most severe reaction to aspergillosis is the formation of granulomas in the lungs.

Otherwise, aspergillosis gives an acute picture - a dense infiltrate forms in the lungs, which disintegrates. With the blood flow, infection of other organs occurs. At the onset of acute aspergillosis, the phenomenon of neutropenia is characteristic, which is expressed in sudden weakness, nosebleeds, fever, sudden chills, severe sweating, tachycardia, and a sharp decrease in pressure. In this case, a decrease in neutrophils is detected in the blood, which makes it difficult for the body to give an inflammatory response to the focus of aspergillosis. Therefore, with neutropenia, it is often not possible to diagnose aspergillosis - all indicators would seem to be normal. However, doctors know from experience that this may signal the onset of aspergillosis, so additional studies are prescribed. Most often, aspergillus settles in the sinuses. In this case, red lesions appear; after the tissue disintegrates, they lose their color and then turn black. This process is very rapid - it usually spreads to the eye sockets, facial tissues, and towards the brain. Typical symptoms in this condition are congestion, pain in the nasopharynx, sinuses, swelling of the mucous membrane. The sinuses are filled with pus, but they do not rupture.

Allergic aspergillosis is often associated with bronchial asthma. In this case, patients note asthmatic attacks, increased eosinophils in the blood, dark areas on x-ray, and the presence of antibodies in the serum (galactoman). To clarify the diagnosis, a sputum analysis is taken. In more than half of patients, aspergillus is detected during culture. In this case, a secondary culture is done to clarify the diagnosis (since conidia could have been accidentally introduced).

Aspergillosis

Main article: Aspergillosis

Pulmonary aspergillosis

Aspergillosis is a group of diseases caused by Aspergillus

.
The most common type of sinus infection associated with aspergillosis is A. fumigatus
.[27] Symptoms include fever, cough, chest pain or shortness of breath, which also occur with many other diseases, so diagnosis can be difficult. Usually only patients with an already weakened immune system or who suffer from other mild conditions are susceptible.

In humans, the main forms of disease are:[28][29]

• Allergic bronchopulmonary aspergillosis, affecting patients with respiratory diseases such as asthma, cystic fibrosis, and sinusitis
• Acute invasive aspergillosis, a form that grows into surrounding tissue, is more common in people with weakened immune systems such as AIDS or chemotherapy patients
• Disseminated invasive aspergillosis is an infection that has spread widely throughout the body.
• Aspergilloma, a "fungal ball" that can form in cavities such as the lungs.

Aspergillus spore found inside 3600-year-old Egyptian Scarab Map Nethert Mudat.[30]
Fungal infections caused by Aspergillus spores remain one of the theories for the illness and untimely death of some early Egyptologists and tomb explorers. Ancient spores that grew on the remains of sacrifices and mummies sealed in tombs and chambers may have been carried and inhaled by excavators, ultimately associated with the concept of the curse of the pharaohs.[31]

Respiratory aspergillosis is also common in birds, and some species of Aspergillus

they are known to infect insects.[7]

Pulmonary aspergillosis

Pulmonary aspergillosis is a very serious diagnosis. Since, due to the development of the disease caused by the mold fungi Aspergillus, aspergillomas begin to form in the human lungs, that is, tumor-like formations that consist of tightly woven fungi. There are also complications such as endocarditis, aspergillus pleurisy, otitis, meningoencephalitis and others.

However, at any time, aspergilloma can cause a serious complication - pulmonary hemorrhage, which can be massive and profuse. And in this case, there is no alternative to surgical treatment. Treatment of aspergillosis with conservative methods is possible when the mucous membranes or skin are damaged by the fungus.

Recommendations

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Symptoms

The most studied form of pathology to date is pulmonary aspergillosis. The initial stages of bronchopulmonary aspergillosis are disguised as a clinical picture of tracheobronchitis or bronchitis. Patients are concerned about a cough with grayish sputum, hemoptysis, general weakness, and weight loss. When the process spreads to the lungs, a pulmonary form of mycosis develops - aspergillus pneumonia. In the acute phase, fever of the wrong type, chills, cough with copious mucopurulent sputum, shortness of breath, and chest pain are noted. There may be a musty odor coming from your mouth when you breathe. Microscopic examination of sputum reveals mycelial colonies and Aspergillus spores.

In patients with concomitant diseases of the respiratory system (pulmonary fibrosis, emphysema, cysts, lung abscess, sarcoidosis, tuberculosis, hypoplasia, histoplasmosis), pulmonary aspergilloma is often formed - an encapsulated lesion containing fungal hyphae, fibrin, mucus and cellular elements. Death of patients with aspergilloma can occur as a result of pulmonary hemorrhage or asphyxia.

Aspergillosis of the ENT organs can occur in the form of external or otitis media, rhinitis, sinusitis, tonsillitis, and pharyngitis. With aspergillus otitis media, hyperemia, peeling and itching of the skin of the external auditory canal initially occurs. Over time, the ear canal becomes filled with a loose grayish mass containing threads and fungal spores.

Aspergillosis may spread to the eardrum, accompanied by sharp stabbing pain in the ear. Lesions of the maxillary and sphenoid sinuses, the ethmoid bone, and the transition of fungal invasion to the orbits are described. Ocular aspergillosis can take the form of conjunctivitis, ulcerative blepharitis, nodular keratitis, dacryocystitis, blepharomeibomitis, panophthalmitis. Complications in the form of deep corneal ulcers, uveitis, glaucoma, and loss of vision are common.

Skin aspergillosis is characterized by the appearance of erythema, infiltration, brownish scales, and moderate itching. If onychomycosis develops, deformation of the nail plates, discoloration to dark yellow or brownish-greenish, and crumbling of the nails occur. Aspergillosis of the gastrointestinal tract occurs under the guise of erosive gastritis or enterocolitis: the smell of mold from the mouth, nausea, vomiting, and diarrhea are typical for it.

The generalized form of aspergillosis develops with hematogenous dissemination of aspergillus from the primary focus to various organs and tissues. With this form of the disease, aspergillus endocarditis, meningitis, and encephalitis occur; abscesses of the brain, kidneys, liver, myocardium; damage to bones, gastrointestinal tract, ENT organs; Aspergillus sepsis. Mortality from the septic form of aspergillosis is very high.

further reading

• Du C, Lin SK, Koutinas A, Wang R, Dorado P, Webb C (November 2008). "Wheat biological refining strategy based on solid-state fermentation for enzymatic production of succinic acid." Bioresource technologies
  .
  99
  (17):8310–5. doi:10.1016/j.biortech.2008.03.019. PMID 18434138.
• Zirbes JM, Milla CE (June 2008). "Steroid-sparing effect of omalizumab in allergic bronchopulmonary aspergillosis and cystic fibrosis." Pediatric Pulmonology
  .
  43
  (6): 607–10. Doi:10.1002/ppul.20804. PMID 18433040. S2CID 25806792.
• Asan A. (February 10, 2015) [2004]. "Aspergillus, Penicillium and related species reported in Turkey" (PDF). Mycotaxon
  .
  89
  (1): 155–7.
• Soltani J (2016). "Diversity of secondary metabolites of the genus Aspergillus". Recent Advances New and Future Developments in Microbial Biotechnology and Bioengineering: Properties of the Aspergillus System and Its Applications
  . pp. 275–292.

Description of appearance

Externally, upon microscopic examination, fungi of the genus Aspergillus are mushrooms consisting of the same type of mycelium, 4–6 micrometers wide, on which “heads” with conidia are sometimes present.

A specific bacteriological nutrient medium for growing colonies of fungi of this genus is the so-called Sabouraud medium. On it, mushrooms form flat colonies, at first white, slightly fluffy, which subsequently take on bluish, yellowish, brown and other colors depending on the species. Their surface becomes powdery.

external reference

• FungiDB: an integrated functional genomics database for fungi and oomycetes
• Aspergillus Genome Resources (NIH)
• Comparative Aspergillus Database Comparative Genomic Resource at Broad Institute
• Central Aspergillus Data Repository
• Fungal Genetics Foundation Center
• Aspergillus/Aspergillosis website Encyclopedia of Aspergillus
  for patients, doctors and scientists
• Aspergillus
  surveillance project in a large tertiary care hospital. (PDF).
• Aspergillus Genome Database
• Mold and mildew

Bibliography

• Centers for Disease Control and Prevention. Brucellosis. Parasites. Link
• Corbel MJ Parasitic diseases // World Health Organization. Link
• Young EJ Best matches for intestinal parasites // Clinical Infectious Diseases. — 1995. Vol. 21. - P. 283-290. Link
• Yushchuk N.D., Vengerov Yu.A. Infectious diseases: textbook. — 2nd edition. - M.: Medicine, 2003. - 544 p.
• Prevalence of parasitic diseases among the population, 2009 / Kokolova L. M., Reshetnikov A. D., Platonov T. A., Verkhovtseva L. A.
• Helminths of domestic carnivores of the Voronezh region, 2011 / Nikulin P. I., Romashov B. V.

An article for patients with a doctor-diagnosed disease. Does not replace a doctor's appointment and cannot be used for self-diagnosis.

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