Latin name: Penicillium glabrum/P.frequentans
A mold, which may result in allergy symptoms in sensitised individuals.
Penicillium is the blue-green mold found on stale bread, fruits and nuts, and used for production of green and blue mold cheese.
Members of the genus Penicillium are almost all filamentous fungi. There are over 200 species, widely distributed in all environments. The most common species include Penicillium chrysogenum (also known as P. notatum), Penicillium frequentans, Penicillium citrinum, Penicillium janthinellum, Penicillium marneffei, and Penicillium purpurogenum. Penicillium molds prefer damp and dark places, but can occur elsewhere. Penicillium dominates in the soils of temperate climates, from which spores are easily released into the atmosphere. The molds are widespread in soil, decaying vegetation and compost, particularly in temperate-zone forests, grasslands and cultivated land.
The species vary from one geographic location to another. For example, P. citrinum is the most prevalent species in the Taipei area, whereas this and P. spinulosum, P. brevicompactum, P. oxalicum and P. chrysogenum were the most frequently recovered species in Topeka, Kansas (1). Species belonging to this genus are prevalent indoor fungi as well (2). Penicillium contrasts with most other molds in that it has no big seasonal variations but reaches peak concentration in the winter and spring. It is a major cause of indoor mold allergy.
Colonies of Penicillium, with some exceptions, are rapidly growing, flat, and filamentous, and velvety, woolly, or cottony in texture. The colonies are initially white and become blue-green, gray-green, olive-gray, yellow or pinkish with time. The colour of the stains is not an accurate guide to the specific molds which have caused them. Penicillium frequentans, for example, produces yellow stains in some instances, pink stains in others.
The contamination of a bacterial culture by a stray asexual spore of P. notatum led to the discovery by Alexander Fleming that a substance was being produced which lysed the nearest organisms, and this led to the development of the Penicillin antibiotic (3). Secondary metabolites from members of the Penicillium genus have been revolutionary in combatting infectious diseases such as pneumonia and gonnorhoea.
Penicillium may be found in vineyards and wine cellars, in the soil of citrus plantations, among all types of stored seeds, and in barns, damp hay, dried fruit and fruit juice. Indoors it is the familiar blue-green mold found on stale bread, citrus fruits, and Apples. It is a contaminant in Rye flour in industrial bakeries. The Penicillium species may also be found in foam rubber mattresses, house dust, stuffed furniture, wallpaper, books, refrigerator doors and rubber tubing. Penicillium may cause the black spots on window sills. Two Penicillium strains are used in making blue and green mold cheese: P. camenbertii and P. roquefortii.
No allergens from this mold have yet been fully characterised.
From studies of Penicillium chrysogenum, a 68 kDa allergen has been detected in this species (4). This appears to be an N-acetyl glucosaminidase and an allergenic heat shock protein belonging to the HSP-70 family (5).
Among the Penicillium allergens, the 32-34 kDa alkaline and/or vacuolar serine proteases have been identified as the major allergens of P. citrinum, P. brevicompactum, P. chrysogenum, and P. oxalicum (6). They have been designated as Group 13 for alkaline serine protease and Group 18 for vacuolar serine protease allergens. As this allergen appears to be common in a number of the Penicillium species, there is a likelihood that it occurs in P. frequentans. This Penicillium allergen has been detected in the sera of about 16-26% of asthmatic patients (6).
An extensive cross-reactivity among the different individual species of the genus could be expected but has not been evaluated in detail.
The 68 kDa major allergen of Penicillium chrysogenum appears to be cross-reactive with P. frequentans and P. roseopurpureum out of the 10 other Penicillium species tested; and Aspergillus fumigatus, Aspergillus terreus and Aspergillus flavus out of 4 Aspergillus species tested; but not to components of 6 other fungi including Alternaria porri, Cladosporium cladosporoides, Aureobasidium pullulans, Fusarium solani, Rhizopus arrhizus and Candida albicans (4).
Although different allergenic profiles were demonstrated in 3 different Penicillium species tested in a study, the results showed that there was an IgE cross-reactivity among the 33 kDa group of major allergens of P. citrinum, P. notatum and P. brevicompactum (7). This may indicate a similar allergen in P. frequentans, and cross-reactivity with this Penicillium species.
Inhalation of Penicillium spores in quantities comparable with those encountered by natural exposure can induce both immediate and late asthma in sensitive persons (8, 22). Sensitivity to the mold Penicillium bears no relationship to sensitivity to the antibiotic Penicillin.
P. frequentans is considered to be the causal agent of cork dust-induced hypersensitivity pneumonitis (suberosis) (9-12). Nevertheless, other fungi can colonise cork during its storage in humid conditions. A fumigatus, Mucor spp. and Rhizopus spp. have also been isolated in cultures of cork sheets or other cork compounds from the workplace. In a study of 8 patients with suberosis, serum-specific IgG antibody determinations and specific skin tests against P frequentans, Aspergillus fumigatus and suberin demonstrated the capacity of both these antigenic extracts to induce an immunologic response (13).
Intradermal skin tests may result in an immediate and a delayed reaction. Precipitins may be found in serum, specific-serum IgG antibody may be detected, and specific bronchial challenge tests may be positive (14).
Esparto grass is a grammineous plant commonly found in Mediterranean countries, and it has a wide variety of uses. Esparto fiber is used for the manufacture of ropes, hemp sandals, rush mats, and decorative stucco plates, and it is used on walls and ceilings. Esparto fibres are also used as support material inside gypsum plaster. The industry is particularly large in Spain. In a study of 20 patients diagnosed with hypersensitivity pneumonitis due to esparto grass exposure, the most frequently isolated fungi in esparto samples were Aspergillus spp. (60%) and Mucor spp. (47%). Specific IgG antibody tests and/or specific bronchial challenge tests were positive for Aspergillus spp., non-fungi-contaminated esparto grass, and other fungi such as P. frequentans and Mucor spp (15).
Sick building syndrome (SBS), first described in 1982, and although no single cause for the above symptoms is likely to be found, the presence of certain molds is becoming increasingly associated with this phenomenon. Symptoms most commonly are fatigue, runny nose, itchy eyes, sore throat, and headaches. Propagules of Penicillium and Stachybotrys species may be associated with sick building syndrome (16-17).
A study found 5 "toxic substances" to which singers presenting at a clinic were exposed while working professionally on the opera stage: aromatic diisocyanates, Penicillium frequentans in cork granulate, formaldehyde in cork granulate, cobalt and aluminum (pigment components), and quartz sand capable of entering the small airways. The study argued that clinical data for some subjects suggested a direct causal link between exposure to 1 or more of these substances and the patients' complaints and the clinical findings. The authors suggested that whenever singers complain about deleterious conditions such as a dry and hot onstage climate, the theatre in question should be investigated (18).
Five workers developed hypersensitivity pneumonitis after working for 5 to 20 years cultivating the edible mushroom shimeji. They began to notice symptoms of cough, sputum, and dyspnoea. Precipitating antibodies were demonstrated to shimeji spore allergens in all of the patients. ELISA studies demonstrated antibodies in the workers to shimeji and to Cladosporium sphaerospermum, Penicillium frequentans, and Scopulariopsis species. The authors concluded that, although it was not clear what causes this disease, these findings may be helpful in determining the specific antigen (19).
Penicillium spp. are commonly considered as contaminants but may cause infections, including pneumonia, particularly in immunocompromised hosts. In addition to their infectious potential, some Penicillium spp. are known to produce mycotoxins (20). For example, P. verrucosum produces the mycotoxin ochratoxin A, which is nephrotoxic and carcinogenic. The production of the toxin usually occurs in cereal grains at cold climates (21). Other mycotoxin-like compounds include patulin, citrinin, citroviridin, emodin, gliotoxin, verraculogen and secalonic acid D (22).
- Shen HD, Lin WL, Tam MF, Wang SR, Tzean SS, Huang MH, Han SH Characterization of allergens from Penicillium oxalicum and P. notatum by immunoblotting and N-terminal amino acid sequence analysis. Clin Exp Allergy 1999;29(5):642-51
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- Diggins FW. The true history of the discovery of penicillin, with refutation of the misinformation in the literature. Br J Biomed Sci. 1999;56(2):83-93
- Shen HD, Choo KB, Chen JH, Lin WL, Chang ZN, Han SH. Characterization of a monoclonal antibody (P40) against the 68 kD major allergen of Penicillium notatum. Clin Exp Allergy 1992;22(4):485-90
- Shen HD, Au LC, Lin WL, Liaw SF, Tsai JJ, Han SH. Molecular cloning and expression of a Penicillium citrinum allergen with sequence homology and antigenic crossreactivity to a hsp 70 human heat shock protein. Clin Exp Allergy 1997;27(6):682-90
- Shen HD, Tam MF, Chou H, Han SH. The importance of serine proteinases as aeroallergens associated with asthma. Int Arch Allergy Immunol 1999;119(4):259-64
- Alenius H, Makinen Kiljunen S, Ahlroth M, Turjanmaa K, et al. Crossreactivity between allergens in natural rubber latex and banana studied by immunoblot inhibition. Clin Exp Allergy 1996;26(3):341-8
- Licorish K, Novey H, et al. Role of alternaria and penicillium spores in the pathogenenis of asthma. J Allergy Clin Immunol 1985;76(6):819-825
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- Avila R, Lacey J. The role of Penicillium frequentans in suberosis (respiratory disease in workers in the cork industry). Clin Allergy 1974;4(2):109-17
- Morell F, Roger A, Cruz MJ, Munoz X, Rodrigo MJ. Suberosis: clinical study and new etiologic agents in a series of eight patients. Chest 2003;124(3):1145-52
- Moral AJ, Arias J, Garcia MA, Abengozar R, Perez-Carral C, Senent CJ. Extrinsic allergic alveolitis caused by Penicillium frequentans. Review and presentation of a case. [Spanish] Arch Bronconeumol 1994;30(9):462-4
- Cruz MJ, Morell F, Roger A, Munoz X, Rodrigo MJ. Hypersensitivity pneumonitis in construction plasterers (espartosis): study of 20 patients. [Spanish] Med Clin (Barc) 2003;120(15):578-83
- Cooley JD, Wong WC, Jumper CA, Straus DC. Correlation between the prevalence of certain fungi and sick building syndrome. Occup Environ Med 1998;55(9):579-84
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- Richter B, Lohle E, Knapp B, Weikert M, Schlomicher-Thier J, Verdolini K. Harmful substances on the opera stage: possible negative effects on singers' respiratory tracts. J Voice 2002;16(1):72-80.
- Akizuki N, Inase N, Ishiwata N, Jin Y, Atarashi K, Ichioka M, Yoshizawa Y, Marumo F. Hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji). Respiration 1999;66(3):273-8.
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