Alternaria alternata

Basics

Alternaria is a genus comprising approximately 50 species {3318; 816; 813}. Among these, A. alternata is one of the most common and most studied fungi of the aeromycota {813; 989}. Alternaria is recognised worldwide as a common plant pathogen and airborne allergen: it is the typical aeroallergen species of the genus and in a majority of cases, is the most frequent species associated with human and animal health problems.

Taxonomy

Comoclathris permunda is the sexual form of Alternaria alternata and Lewia sp. is the sexual form of many other Alternariaspp.  {3842} ; other teleomorph genera are Graphyllium and Pleospora.

It is said that there are 44 definite, well-known species, but there may be hundreds more; in fact the Universal Protein Resource data library lists 95 named species in its registry among 433 registered strains {3318}.  Some authorities also suggest that A. alternata is a species complex rather than a single species and could consist of several heterogeneous species {816}.

Habitat/Ecology

Alternaria spp.are cosmopolitan dematiaceous fungi commonly isolated from plants, soil, food and indoor air environment. Alternaria species are known as major plant pathogens {1635; 725}  and saprophytes on many substrates {816; 1056; 3729; 725}. They are ubiquitous in the environment and are a natural part of the fungal flora worldwide. They are normal agents of vegetable matter decomposition. The spores are airborne and found in the soil and water, as well as indoors.  They are often found in a large proportion of air samples but at concentrations below 10% of total counts. 

Growth requirements

Alternaria grows on a variety of substrates. Temperature requirements are between 2 and 32 °C (optimum 25-29 °C) {1056; 725} . The optimal pH is between 4 -5.4, although this species may grow on a pH range of 2.7 to 8 {989} . The minimum available water (Aw) requirements range between 0.85 and 0.88 depending on the species {813; 989}.

Water Activity :      Aw =     0.85 – 0.88   

Growth on building materials or indoor environment

Alternaria sp. has been reported worldwide in the indoor environment in air, surface and dust samples {1584; 624; 2388; 605; 1756; 2193}.  Alternaria is a secondary colonizer {587} and grows on various building materials and indoor substrates. It is often found on floors, in carpets and mattress dust;  it can establish itself on damp window frames and window putty, walls and ceilings, wallpaper and acrylic paint finishes as well as in humidifier water and ventilation filters ; it also contaminates textiles (cotton, jute, wool), rubber, magnetic tapes, negatives and oil paintings, paper, parchment and certain synthetic materials {989; 1056; 3729; 725}.  

Alternaria is a frequent contaminant in water-damaged or flooded buildings {695; 720}.  

Laboratory section

Normal laboratory precautions should be exercised in handling cultures of this species within Biosafety Level 2 practices and containment facilities.

Colony, macroscopic morphology

Alternaria grows rapidly and matures within 5 days {412}; colony size reaches a diameter of 3 to 9 cm following incubation at 25 °C for 7 days on potato glucose agar (PGA) {816}. The colony is flat, downy to woolly and covered by greyish, short, aerial hyphae, becoming in time greenish black or olive brown with a light border {412}. The reverse side is typically brown to black due to pigment production {816; 412} .  When grown on malt extract agar (MEA) at 25 °C, colonies reach a diameter of 6 cm within 7 days, being black or greyish {989; 725} . On potato carrot agar (PCA) medium at 25 °C they attain a diameter of 5.5 to 6.0 cm in 7 days; the mycelium is hyaline with black or olivaceous-black conidia {1056} .

Microscopic morphology

Hyphae are septate and dark. Conidiophores are short (40-70 x 3-4 µm), also septate and brown in color, occasionally producing a zigzag appearance. The simple or branched conidophores bear large ovoid or ellipsoid conidia (7-10 x 23-34 µm), which have both transverse and longitudinal septations. These conidia may produce germ tubes and are ovoid to obclavate, darkly pigmented, muriform, smooth or roughened. The end of the conidium nearest the conidiophore is round while it tapers towards the apex, hence giving the conidia a typical beak or club-like appearance {816; 989; 412}.

Specific metabolites

Organics compounds (including VOCs)

There are no reports of volatile organic compounds specific to Alternaria sp. that could be detrimental to human or animal health. 

In the indoor environment of damp buildings, many metabolites, including microbial volatile organic compounds (mVOCs), have been identified as common to several fungal species. The frequent presence of Alternaria in mouldy buildings could contribute to the concentration of these metabolites indoors {3717} and to the occurrence of sick building syndrome {569; 2649}.

Some very potent enzymes produced by Alternaria species, especially cellulases, easily decompose the cellulose components of the contaminated material {725}.  Some species also produce proteases and amylases {989}.  The production of a melanin-like pigment is one of the characteristic metabolites of Alternaria sp.

Mycotoxins

Alternaria spp. produce a unique group of mycotoxins, including alternariols, altenuenes, altertoxins and tenuazonic acid {813; 989; 603; 725}. These mycotoxins may be produced in tomatoes, apples, olives, wheat, sorghum, sunflower seeds and pecans. Tenuazonic acid is an important mycotoxin that is also produced by another fungus, Phoma sorghina {715}.

Building materials artificially contaminated with a variety of fungi, including Alternaria sp,, have been studied for their toxic properties {603};  five out of six isolates of Alternaria spp. produced alternariol and alternariol monomethyl ether.

The production of mycotoxins by Alternaria alternata on cellulosic ceiling tiles was examined by thin-layer chromatography and high-performance liquid chromatography. Alternariol and alternariol monomethyl ether were found in ceiling tile extracts, whereas extracts of control rice cultures of all three isolates also produced these mycotoxins in addition to altenuene and altertoxin-I. Extensive fungal growth and mycotoxin production occurred in these ceiling tiles at a relative humidity of 84-89% and 97% {796}.  In controlled studies, 25°C appeared as the optimum temperature for the production of the 3 toxins alternariol, alternariol methyl ether and alternaric acid {3873}; hence suggesting that indoor conditions can be favourable to toxin production.

Adverse health reactions

Irritation and inflammation

In the indoor environment of damp buildings, many organic compounds, including microbial volatile organic compounds (mVOCs), have been identified associated with several fungal species. Some of these compounds are common to most fungal species and probably contribute to various health problems associated with indoor air quality.
However many of the fungal metabolites identified are non reactive and are in low concentrations in indoor air {594}.

Alternaria produces some mVOCs that are common to many moulds {3717; 3858; 1840; 2749} and may contribute to the occurrence of irritation symptoms observed in sick building syndrome {569; 2649}. The complete specific mVOC profile ofAlternaria alternata is not yet published.

Allergic reactions

Alternaria spp. components are recognised potent allergens.  The relatively large abundance of Alternaria conidia in outdoor air and its occurrence in mouldy houses makes this fungus one of the most important fungal allergen sources {989; 39; 2355; 2285; 808}. This worldwide allergen generates high prevalence sensitisation: depending on the geography and populations studied, the prevalences of positive skin tests (ST) are 3% to 12% in the general population and 13% to 39.4% in atopic subjects (Simon-Nobbe 2007 {3911}).  In one study conducted in a large cohort of patients presenting respiratory symptoms (asthma and allergic rhinitis), a 66% incidence of Alternaria sensitisation was observed in the group of patients that had one or more positive fungal ST {3207}.

In particular, Alternaria alternata sensitisation is responsible for Type I allergic reactions {1635; 2285}, rhinitis {648}, asthma and allergic sinusitis {2558; 3802; 166}.  A. alternata is associated with asthma exacerbations {2641; 824; 1780; 3896; 3910; 3904; 3907} and even with onset of asthma {3902}; life threatening exacerbations have sometimes been associated withAlternaria sp. {1085}.

Allergic components and mechanism

The many biochemical studies and pathophysiologial modelling of Alternaria allergenic properties reflect the importance of this ubiquitous fungus. The major allergens of A. alternata have been isolated and 13 recognised fractions have been well characterised; moreover, it has been shown that wherever A. alternata conidia have been isolated in the world, they always contain the same allergens. Alt a 1 is the major allergen : it is responsible for 98% of A. alternata sensitisations {2642}. Closely related moulds, such as Cladosporium herbarum and Ulocladium species, also contain some  allergenic fractions identical to those found in A. alternata {3760; 3912; 725}. 
At least 35 Alternaria species, other than A. alternata, have been characterised as allergens and have been shown to cross react within the phylum {3912}.

Immunological mechanisms involved in IgE  production have been extensively investigated {3911} {3877; 2676; 2642; 3905; 3799} .  

Toxic effects (mycotoxicosis)

Ingestion of Alternaria toxins has been implicated in animal and in human health disorders {3748} but very few cases are reported in the literature. Surveys to date have shown that occurrence in food is very low, hence there are currently no official guideline limits on these mycotoxins.

Outbreaks of mycotoxicosis in farm animals in Germany have been linked to cereals contaminated by Alternaria toxins.  

Moreover, contamination of cereal grains by Alternaria mycotoxins could explain the aetiology of Kashin-Beck Disease (KBD). A non-identified Alternaria metabolite has been detected in barley samples stemming from symptomatic families {Haubruge, 2001 3847 /id}; however, the role of Alternaria could be only secondary to that of Trichothecium roseum and Dreschlera sp. which may be more closely associated with this disease {1838, Chasseur, C., 2001}.

Occupational acute toxic lung injury has been attributed to Alternaria alternata in early stages of organic dust toxic syndrome (ODTS) {2672}. 

Alternaria mycotoxicosis through inhalation has yet to be confirmed. Lower respiratory symptoms in children exposed to a mouldy indoor environment have been well documented. Whether fungal toxin exposure contributes to this association is uncertain. Some authors suggest that these lower respiratory illnesses in children and some sick building syndrome cases could be in part attributable to fungal components of Alternaria (glucans and proteins) and to mycotoxin exposures, although actual mechanisms remain unknown {1087}.

However, many controlled studies have been undertaken either in vitro at the cellular level or in animal models and have characterised the toxic properties of these Alternaria metabolites.   

Infections and colonisations

While infection with Alternaria is seldom reported, it can no longer be considered as rare. Alternaria spp. have emerged as opportunistic pathogens particularly in immunosuppressed patients, such as transplant recipients and patients with haematologic malignancies and other cancers {2671; 2031; 1792; 3808}{Morrison, 1993 3931 /id}.   In these immunocompromised patients, simple colonisation may lead to the development of invasive disease {816}.

Alternaria alternata may cause upper respiratory infections in AIDS patients {3809}.

Alternaria sp. is considered one of the causative agents of phaeohyphomycosis {2865}. Cases of onychomycosis, sinusitis, ulcerated cutaneous  and subcutaneous infections, and keratitis, as well as deep sited soft tissue infections and osteomyelitis due to Alternaria sp. have been reported  {3832; 1598; 2645; 2683; 2674; 2684; 3818; 3821; 3817; 3671; 3811; 3807; 3800; 166}{Schell, 2000 3932 /id}.   

Virulence factors

No special virulence factor has been reported.  Important subcutaneous lesions and nail infections are associated withAlternaria, even though most species do not grow at 37 °C {813}.

Specific settings

Nosocomial infections

Alternaria has been found in the hospital setting {313; 386}, but no confirmed case of nosocomial infection due to Alternariahas been reported in the literature .  However some authors consider that opportunistic infections due to Alternaria could become an emerging problem for immunocompromised patients in the health care setting {1747; 366}.   

Occupational diseases

In the workplace, Alternaria sp. has been associated with occupational asthma in bakers {2001}{2401; 2989} and with organic dust toxic syndrome (ODTS) reactions in cotton handlers {2672}. In the agricultural setting as well as in compost and sewage treatment facilities {855}, high concentrations of Alternaria on plant or waste material may increase the risk for Type I allergic reactions and Type III HP or farmer’s lung disease {725}{1777; 1778; 2680; 2658; 1822}. Alternaria inhalation may also be associated with woodworker’s lung and apple store hypersensitivity xxxxxxxxxxxxxxxx {813}.

In some instances, workers handling plant material could be at higher risk for superficial infections due to introduction of this fungus through skin abrasions or puncture wounds {2546}. 

Diagnostic tools

Cultures

Since Alternaria species are cosmopolitan and ubiquitous in nature, they are also common laboratory contaminants. Thus, their isolation in culture requires cautious evaluation {1819}.  The presence of Alternaria in sinus fluids may be compatible with chronic rhinosinusitis, but can also be a fortuitous finding {2678}.

Histopathology

Dark coloured filamentous hyphae are observed in Alternaria-infected tissue sections stained with H&E. If pigment formation is not obvious, Fontana-Masson silver stain, which is specific to melanin, may be applied {816}.

Vegetating lesion on forearm, with mammiliate surface, resulting from a subcutaneous lesion caused by Alternaria alternata{2674}.

Fungal structures in a granulomatous inflammation in the dermis caused by A. alternata (Periodic acid-Schiff after diastase digestion (x 1700){2674}.

Immunodiagnosis

The Alternaria extracts for in vitro and in vivo testing are available commercially and can be useful in establishing an association between an allergic reaction (IgE) or hypersensitivity pneumonitis (IgG) and Alternaria exposure. 

Alternaria allergen extracts are part of the basic testing panels as single antigens or as part of antigen pools.  The most common commercially available allergen preparations for use in vivo and/or in vitro are:  Alternaria sp. extracts for in vivotesting, i.e.  skin tests, and Alternaria alternata  alt-1 for in vitro testing such as RAST.

More details

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