Penicillium spp.

Penicillium spp. on gypsum boardPenicillium spp. on woodPenicillium spp. on a ceiling tilePenicillium spp. on EM agarPenicillium spp. on RB agarPenicillium spp. - Microscopy (EM Culture)

Basics

There are over 200 named species of Penicillium. Over 20 are mentioned regularly as found in the indoor environment {1056, 470, 2694}. Many species of Penicillium adapt easily to indoor parameters and grow well on building materials. Therefore, it would be impossible to list them all in the context of this document. We will mostly address the Penicillium genera (P. spp.) as a whole while mentioning certain species when needed.

Taxonomy

Kingdom Fungi Order Eurotiales
Phylum Ascomycota Family Trichomaceae
Class Euascomycetes Genus Penicillium

Many Penicillium are hyaline hyphomycetes anamorphs: some Penicillium spp. have known telemorph forms included in the genera EupenicilliumTalaromycesHamigera, and Trichocoma {3133}.

Habitat/Ecology

Penicillium are very commonly found in soil, on decaying vegetation and compost or on wood, dried foodstuffs, spices, dry cereals, fresh fruit and vegetables {808, 3095}they are also found growing on building materials in water-damaged environments {413} as well as in indoor air and house dust.

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Penicillium species are one of the most common causes of spoilage of fruits and vegetables. For example, Penicillium italicum and Penicillium digitatum are frequent causes of rot of citrus fruits, while Penicillium expansum is known to spoil apples and {798, 2539,3090}.

Penicillium is among the five most common genera in the outdoor and indoor fungi aerosols {2649, 2747, 2759}. It is consistently found year-round in the outdoor air, but concentrations vary seasonally and compose a small proportion of the natural aerosolised fungal flora in northern climates: Penicillium prevails in the autumn and winter months, although present year-round {3012, 624, 2014}.

Growth requirements

Penicillium spp. are mesophilic fungi, growing between 5-37°C (optimal, 20 – 30°C) at pH 3-4.5. Maximum growth in vitro is obtained at 23°C at pH 3-4.5.

Water Activity: 0.78 - 0.88 {808}

Growth on building materials or indoor environment

Penicillia have been found in up to 53% of contaminated homes before remediation in significant amounts {1582}.Penicillium spp. are reported to colonize absorbent materials such as wallboard {3055}, insulation material {3004, 3014}, fibreglass duct liner of the HVAC systems {3005} and carpeting {1072}.

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A Scandinavian study showed that products most vulnerable to mould attacks were water-damaged, aged organic materials containing cellulose, such as wooden materials, jute, wallpaper, and cardboard. The microfungal genus most frequently encountered in these substrata were Penicillium (68%) {605}.

Studies have demonstrated that certain species of Penicillium are able to grow on building materials such as wallpaper, drywall, and cellulose-containing ceiling tiles, particularly after water damage and flood have occurred {3044, 695, 315). Also, wet spray-applied cellulose insulation (WSACI) supports significant levels of Penicillium contamination {670}. Growth of P. chrysogenum, on this type of insulation in water-damaged buildings, may give rise to very high mould concentration (2 millions spores/g of bulk sample) {670}. Besides damp insulation and cellulose, carpeting is also easily contaminated mainly by Penicillium spp. {1072}.

In a controlled study of mould growth, Penicillium was visually detected at 2 weeks on untreated gypsum boards {587}. Penicillium, Cladosporium, and Acremonium were early colonizers of untreated panels. Apart of the visible growth, these fungi are often found in wall cavities and can be difficult to detect {2069, 3081.

Penicillium chrysogenum is a major indoor fungus regarded as one of the primary wall colonizers in water-damaged buildings {911}. This mould is the most widely encountered Penicillium species in the built environment {951}. It is often found in mouldy buildings where it destroys different building materials, e.g. wallpaper. It also grows well on the glue on the reverse side of the wallpaper and on moist chipboards and is found in paints {725}.

Penicillium is reported, in conjunction with Aspergillus and/or Cladosporium and/or Paecilomyces, as the principal contaminant found indoors following a flood {620} or firefighting efforts {3067,2841} or in buildings with chronic moisture problems {575}. Penicillium spp. are also constantly detected in air and surfaces sampled in swimming pool areas {1578}.

One must remember that indoor total airborne fungal concentrations depend on sources and extent of dampness in the building as well as type of wall and floor coverings, aeration levels and overall cleaning frequency and presence of pets {624, 2747}. Also bearing in mind that seasonal fluctuations and outdoor environment linked levels largely contributed to the variability of the base line flora indoors {3021}.

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

Taxonomy of the Penicillium genera is particularly complex and difficult to master. Accurate identification based on solely macro- and micro-morphological criteria remains difficult, though possible. However, some common traits are shared by the more prevalent indoor species {1056}. Colonies are usually fast growing, in shades of green, sometimes white or occasionally other colours, mostly consisting of a dense felt of conidiophores. The surface often exhibits some exudates and the reverse side can be pale to yellowish in colour.

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Colonies grow rapidly on standard culture media. Colonies are flat, velvety to cottony (or lanose) to funiculose (cord-like) in texture, initially white or light hues of green; at maturity, exhibit a wide range of colours, most often with some shade of green. They may be blue to green, olive grey, yellow or even pinkish. Many species produce droplets of coloured or hyaline exudate.

P. chrysogenum colonies grow rapidly to 4-5 cm within 10 days, at 25 °C on Czapek agar. The colonies are flat, either velvety to cottony in texture, initially white or pale yellow-green, becoming blue and green, olive grey, yellow or pinkish in time; a broad white mycelium margin appears raised; numerous yellow exudates as yellow droplets, sometimes hyaline or absent. Odour is usually aromatic, fruity. The reverse is usually pale to yellowish {989, 816, 814, 724}.

Microscopic morphology

Septate hyaline hyphae (1.5-5 µm in diam.) bear branched or unbranched conidiophores. The first cell of the conidiophore is named stipe; the secondary branches are known as metulae. Metulae are more or less cylindrical, smooth-walled and bear 3 to 6 flask-shaped phialides {816, 412, 724}, giving rise to long dry chains of small round to oval spores (2,5-5µm). The branching pattern allows the strain to be classified into categories.

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When the stipe ends directly into a penicillus of phialides, i.e. without branching, the strain is said to be monoverticillate. If the penicillus is branched, it can be one-stage (biverticillate), two-stage (terverticillate) or three-stage branched (quaterverticillate) Penicillia.

Conidia are mostly subglobose to broadly ellipsoidal, rarely cylindrical or fusiform; conidia are small, 2.5-4 µm, hyaline or slightly greenish, smooth-walled, usually produced in divergent chains or loose columns {725, 816, 814, 724}.

Penicillium single spores are indistinguishable from Aspergillus spp. or other genera with small round to oval colourless or slightly pigmented spores. Thus, on direct examination of air samples, these spores are reported as Asp/Pen spores.

Microscopically, chains of single-celled conidia (ameroconidia) are produced in basipetal succession from a specialized conidiogenous cell called a phialide. The term basocatenate is often used to describe such chains of conidia where the youngest conidium is at the basal or proximal end of the chain.

In Penicillium, phialides may be produced singly, in groups or from branched metulae, giving a brush-like appearance known as a penicillus. The penicillus may contain both branches and metulae (penultimate branches which bear a whorl of phialides). All cells between the metulae and the stipes of the conidiophores are referred to as branches. The branching pattern may be either simple (non-branched or monoverticillate), one-stage branched (biverticillate-symmetrical), two-stage branched (biverticillate-asymmetrical) or three- to more-stage branched.

Conidiophores are hyaline and may be smooth- or rough-walled. Phialides are usually flask-shaped, consisting of a cylindrical basal part and a distinct neck, or lanceolate (with a narrow basal part tapering to a somewhat pointed apex). Conidia are globose, ellipsoidal, cylindrical or fusiform, hyaline or greenish, smooth- or rough- walled. Sclerotia may be produced by some species {1056}.

Specific metabolites

Penicillium is most well-known as the first antibiotic producer {901, 877}. But, in fact, Penicillium spp. can produce many organic compounds and a large number of specific metabolites, including some with antibiotic and antiviral activity and some potent toxins.

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P. chrysogenum, formerly called P. notatum, is a common species, the well-known source of penicillin {901, 877}. In 1928, Alexander Fleming’s bacterial cultures were contaminated by airborne spores of a green mould. Fleming noticed that bacteria were not growing close to the green mould. He concluded that the mould was producing a compound that was killing or inhibiting the growth of bacteria. That is how penicillin, the oldest and probably the best-known of all the antibiotics, was accidentally discovered.

Organics compounds (including VOCs)

Penicillium spp. produce various hydrocarbons, alcohols, ketones, esters and terpenes in nature as well as on building materials {594, 2076}. Commonly produced metabolites are alcohols such as 2-methyl-1-propanol, 3-methyl-1-butanol, 1-hexanol, as well as 2-heptanone, 2-pentanone and 2,5-dimethyl-furan {607}. Some Penicillia produce 2-methyl-isoborneol, giving off a heavy musty odour. The mVOC production is influenced by both medium and species.

A number of organic compounds, including volatile organic compounds (VOCs), have been identified in indoor air in damp buildings, which are thought to contribute to different health problems linked to indoor air quality. Most of identified metabolites are non-reactive and found in low concentration in the indoor air {594}.

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Some species have a defined mVOC profile which may be subjected to considerable modification in response to external factors such as cultivation on different substrata. In fact, the cultivation on different substrata changes both the number and concentration of mVOCs {2968,1148,2809}. Some volatiles are specific for single species of Penicillium {2809} whereas others can be produced by many species.

P. chrysogenum is known to produce dozens of organic acids, amino acids and enzymes. Among VOCs, P. chrysogenum produces mainly C2-C4 compounds, isopropene, alcohols, terpenes, octadienes and methyl ketones: at least, 30 specific compounds were identified {947}.

P. chrysogenum is able to produce many VOCs when experimentally growing on buildings materials like plaster board and new cardboard material {947}. However, the secondary metabolite production is lower on building materials compared with rich laboratory medium {603}.

Penicillium commune produces on pine wood and gypsum board metabolites such as 3-methyl-l-butanol, 2-methyl-l-butanol, 2-methyl-1-propanol, 2-butanone and l-methoxy-3-methylbutane. On pine wood, alcohols were the dominating compounds, and geosmin was the main product in cultivation on gypsum board-mineral wool. Consequently, the cultures on gypsum board-mineral wool had a strong earthy smell.

A study of Penicillium commune and Paecilomyces variotii shows that several compounds are produced when these moulds are cultivated on pine wood {607}. On gypsum board-mineral wool only, 2-methyl-l-propanol was found from both species. Scsquiterpenoid compounds were the main products from both species on this medium. On pine wood, no terpenoid compounds produced by the fungi could be detected.

Cyclopenol, cyclopenin, and penitrem A (see mycotoxins) are characteristic for certain Penicillia and were found in conidial extracts; they are, therefore, assumed to occur in native bioaerosols {1148}.

Aerosolised Penicillium propagules have been reported as associated with SBS {2649}. Yet even when dense fungal growth was observed on surfaces within the heating-cooling system, most room air samples yielded fewer than 200 CFU m³ {3005}. Insulation contamination may lead to secondarily contamination air-handling units {527} releasing fungal metabolites such as acetone and a carbonyl sulphide-like compound {3004}.

Mycotoxins

Many species of Penicillium are common contaminants on various organic materials and are recognized potential mycotoxin producers. Among the best studied mycotoxins produced by P. spp. are: aflatoxin, citreoviridin, citrinin, citromycetin, erythroskyrin, frequentin, gibberelin, griseofulvin, hadacidin. kojic acid, luteoskyrin, mycophenolic acid, ochratoxin A and B oxaline, parulin, patulin, penicillic acid, penitrem-A-F, riboflavine, roquefortine, rubratoxin, rugulosin, rugulovasine, thomitrems A and E, tremorgenic mycotoxins (penitrem, territrem, verruculogen), verrucosidin, viomellein, viridicatin, xanthocilline, xanthomegnin (ref AMC) {989, 3102, 927, 3176}.

Most of these toxins are associated with food and grain spoilage. Some Penicillium mycotoxins have been studied in case of indoor building contamination and have been found in natural water damage circumstances or in simulation models delmulle 2006 sumarah mw 2005 rhea 2003 {795, 216, 603, 3087}.

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The most well-known toxin producing species in foods include P. citreonigrum, P. citrinum, P. crustosum, P. islandicum and P. verrucosum. Because of the many toxigenic species and the variety of toxins produced, it is often important to identify Penicillium strains at the species level when it comes to food contamination.

P. chrysogenum is reported to synthesize some alkaloid mycotoxins and some related to the sterol group like fungisterol; it can also produce toxins such as roquefortine C on substrates other than food {877, 997, 2607, 2826}.

Roquefortine C has been isolated from Penicillium roquefortii which is industrially used for blue cheese production. Under normal cheese production conditions, this compound is not produced in dairy products {950} but may be found on other substrates.

Ochratoxin A (OTA) is a mycotoxin produced by Penicillium and Aspergillus species, which contaminates many food commodities {3008}. Indoor building materials heavily colonized with Penicillium and other fungi have been reported to contain mycotoxins and exposure to airborne dust and fungal conidia could be sources of OTA {606}. Peak exposures to airborne OTA may be significant, e.g., in agro-food environments {1220, 1550}.

Most strains of P. citrinin produce penicilinic acid and citrinin on carbohydrates such as starch {3034}. Patulin and citrinin are also found in extracts from apples stored at 25 °C for 12 days after inoculation with Penicillium expansum {3090}.

Strains of Penicillium expansum are the main producers of patulin in nature: this mycotoxin occurs during fruit spoilage. Patulin is a major concern with regard to human health because exposure can result in severe acute and chronic toxicity, including carcinogenic, mutagenic, and teratogenic effects. Potentially toxic patulin levels are in the range of 75 to 396 g/ml {3197, 3198}.

Some strains of indoor air isolates of Penicillium chrysogenum produce, at certain temperatures, a proteinaceous hemolysin, chrysolysinTM. Cell-line studies suggest that chrysolysin might act to promote the host's inflammatory response after P. chrysogenum exposures by triggering the production of the macrophage inflammatory protein-2 (MIP_2) {1534}.

Adverse health reactions

Health risks associated with mould exposure in water damaged buildings are well-established, especially for upper and lower respiratory tract symptoms. Penicillium being among the most prevalent indoors, it can significantly contribute to different indoor air problems.

Irritation and inflammation

Generally speaking, all moulds contain substances that are irritant and promote inflammation to some degree. Some VOCs produced by moulds in the indoor setting on damp building materials are thought to contribute to different health problems, such as eye irritation, irritation of the nose and throat, lethargy and headache {594}. In vitro and in vivo studies demonstrate that Penicillium sp spores and spore extracts can experimentally induce significant immunomodulatory response in lung cells and inflammation in animal models {951}.

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The non-specific (1-3)-beta-D-glucans are non-allergenic structural cell wall components of most fungi that have been suggested to play a causal role in the development of irritative respiratory symptoms associated with indoor fungal exposure {1346}.

Moreover, roquefortine C can stimulate inflammatory responses in vivo and might explain some of the indoor effects associated with P. chrysogenum spores exposures. Specifically, it causes elevated macrophage, neutrophil, interleukin and tumour necrosis factor concentration in the bronchoalveolar lavage fluid experimentally in mice {951}.

Allergic reactions

Penicillium spp. constitute very common outdoor and indoor aero-allergens linked to Type I allergies, hay fever and asthma {2342, 3095}. Bronchial challenges with Penicillium spp. spores induce immediate-and delayed-type asthma in sensitised subjects {3166}. Mould sensitisation may be associated with severe asthma attacks requiring hospital admission {824}. In some patients, Penicillium may trigger an IgE-mediated reaction that may contribute to the exacerbation of eczema.

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Caution must be taken when interpreting clinical relevance of serologic measurements of fungal IgE-antibodies for dermatology patients {2280, 3209}.

Penicillium spp. have been repeatedly found, sometimes in conjunction with Aspergillus, as the dominating type in indoor air samples of asthmatic mould-sensitive patients {3011, 623, 3022, 1566, 819, 3078}. Penicillium, alone or in combination with Aspergillus, is known to sensitise infants {2669}, children {915, 2750} and adults {915, 776, 917, 855} as shown by skin tests or serology. Exposure to high levels of Penicillium are a significant risk for wheeze and persistent cough {1393, 913, 3029}. Among other indoor environmental factors, Penicillium exposure has been linked to both sensitisation and allergic symptoms among children {3015} and adults {3066} and has been positively linked specifically to asthma in children {2750}.

Allergic components and mechanism

p>Many Penicillium species have IgE sensitising and binding properties; some of the mentioned species are P. chrysogenum, P. citrinum, P. notatum, P. oxalicum and P. brevicompactum {3080, 3079}. Other Penicillium are also well-identified as allergens: P. viridicatum, P. expansum, P. oxalicum, P. paxilli, {854} P. notatum (cross-reacting with P. camembertii) {3167, 2239}, P. simplicissimum {1108} and P. luteum {1288}.

 

Moreover, many specific fractions of Penicillium extracts have been identified as allergens.

P. chrysogenum is reported to be one of the four fungi considered to be most allergenic {624}. Conidia less than 5 ?m in size are able of being suspended in air for hours and can be inhaled into the lower respiratory tract (903). This species is known to have several allergens (serine proteases and glycoproteins) and can induce allergic responses in animal models; at least three proteins have been identified as allergens by examining reactivity with IgE antibodies in sera from asthmatic patients {909}.

Molecular biology has allowed extensive biological and immunological characterization of extract fractions of different species of Penicillium. Studies have been carried out on many species and fractions. For example, here are some of the allergenic components studied: serine proteases Pen ch 13 and Pen ch 18 (Pen n 18) from strains of Penicillium chrysogenum (P. notatum), Pen b 26 from P. brevicompactum, Pen o 18 from Penicillium oxalicum, Pen c 24 from P. citrinum.

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P. chrysogenum conidia release proteolytic enzymes which have been shown to both induce and propagate allergic inflammation in a mouse model. Intraperitoneal injections of Penicillium extracts from viable conidia in mice induce significant increase of total serum immunoglobulins IgE and IgG; bronchoalveolar lavage cell counts revealed increased number of eosinophils and neutrophils. Histopathological examination of lungs detected perivascular inflammation by eosinophils and neutrophils and increased mucous production. Non-viable conidia do not seem to induce the same allergic reactions {925; Instanes, C. et al. 2004a}. Living in an environment with moulds can induce not only specific allergy to mould allergens but also increase allergy to other environmental allergens {945, Instanes, C. et al, 2004}.

Exposure to Penicillium spp. spores does occur outdoors, but this exposure is far less important than what occurs indoors in a contaminated building or in some occupational settings {27}. Long term exposure to high concentrations of P. chrysogenum, such as found in contaminated buildings, can produce significant levels of total IgE.

In fact, a controlled study has shown that long term (6 weeks) intranasal instillation of P. chrysogenum viable conidia, at concentrations comparable to exposures found in contaminated buildings (1 x 104 conidia), produces significant levels of total IgE, while instillation of non-viable conidia did not show significant changes in total IgE; an increase of IgG (as compared to controls) was observed in both cases {918}. Long term inhalation of viable conidia can induce inflammatory responses like those observed in allergic asthmatic reactions. With low numbers of viable conidia (1 x 102), mice did not develop allergic symptoms, indicating that exposure to low levels of viable conidia similar to those in non-contaminated buildings do not induce allergic sensitisation {903}.

Hypersensitivity pneumonitis

Type III hypersensitivity pneumonites due to Penicillium are well-known in occupational setting: some are listed in the International Classification of Diseases (ICD-10-CA) under the heading J67. Specific agricultural occupational (see occupational section) as well as indoor exposures are known to lead to HP. Many species of Penicillium have been linked to HP symptoms. Fatigue, dyspnoea and low grade fever related to specific working environment have been linked to Penicillium exposures such as P. camembertii, P. notatum {3054}, P. roquefortii {3239} and P. verrucosum {3034}.

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Different fungi present in the water can illicit a syndrome, known as “humidifier lung” disease, in exposed subjects: studies have shown that close to a quarter of symptomatic subjects have specific IgGs directed against Penicillium notatum extracts from water systems {3010, 277}. Other indoor environmental exposures to Penicillium spp. have been associated with fungal HP {3014, 1403}.

Toxic effects (mycotoxicosis)

Most Penicillium species are active producers of toxins under given sets of growth conditions. Toxic effects due to ingested Penicillium toxins include cytotoxic, nephrotoxic and tremorgenic effects as well as immunosuppressive and carcinogenic effects. These pathologies are well-known to occur in man, livestock and other animals {3182, 3184, 3185}. Consequently, contents of some toxins in livestock feed and food for human consumption are strictly regulated {3191, 3190, 3189}.

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Ochratoxin A, which is nephrotoxic and carcinogenic, may be produced by P. verrucosum. Verrucosidin is another mycotoxin produced by this fungus that exhibits neurotoxicity. Penicillic acid is another mycotoxin which is nephrotoxic and may cause liver damages.{801,1550} .

Roquefortine C is considered as a cytotoxic and relatively weak neurotoxic substance, {948} as mentioned in the metabolite section. Roquefortine C is mostly recognized as a toxic compound in animal food, where it has been involved in livestock mortality {950}. Keblys et al {948} demonstrated that roquefortine C can cause, in vitro, inhibition of isolated porcine lymphocytes. However, Bünger et al {949} assert that roquefortine C has an insignificant toxicity on humans after ingestion. They found no cytotoxicity up to the limit of solubility; this apparent lack of toxicity may be due to low bioavailability.

The study of a cluster of human neoplasms and cattle leukemia has shown the presence of Penicillium meleagrinum in the living environment as a possible risk factor for these cancers {2416, 1826}.

Experimental studies on house dust have shown that chloroform-extractable exo- and endometabolites have very potent ciliostatic effects on chicken trachea. {3181, 3179, 3180}. Metabolites of Penicillium spp., isolated from tested house dust, showed the highest toxicity in vitro in these studies {550, {Pieckova, E. et al. 2004; Pieckova, E. et al. 2002}.

Infections and colonisations

Human infections by Penicillium spp. are rare; however, opportunistic infections leading to respiratory infections, mycotic keratitis, otomycosis and endocarditis have been occasionally reported. Bronchopulmonary infections have been the most frequently reported form of the disease {3215} and asymptomatic pulmonary nodules have also been reported {3216}.

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A literature review done on a fifty year period shows the diversity of these infections. From 1951 onwards, 31 reported cases of invasive disease included 12 cases of pulmonary infection (6 in non-immunocompromised patients), 4 cases of prosthetic valve endocarditis, 6 cases of CAPD peritonitis, 5 cases of endophthalmitis, individual cases of fungemia and oesophagitis (both in AIDS), upper urinary tract infection and intracranial infection. Trauma, surgery or prosthetic material is commonly implicated in the non-pulmonary cases. Superficial infection (keratitis and otomycosis) is commonly caused by Penicillium spp. {3242}. Reports of rare cases of invasive disease also include a case of pulmonary infection caused by Penicillium spp. in a patient with chronic granulomatous disorder (CGD), a case of cerebral disease caused by P. chrysogenum from an unknown source and an acquired infection caused by P. decumbens peri-operatively with paravertebral infection. Isolated cases of corneal ulcers, bladder wall infection (gallium j 1951) and chronic mastoïditis {319}, as well as a case of invasive infection by P. sp (that could have been a P. marneffei) were reported in an acute leukemia patient {3220}.

The many anatomic sites infected suggest that the organism could disseminate through haematogenous as well as through direct mucosal invasion {901}.

More recently, pulmonary and disseminated infections by P. marneffei have been reported in AIDS patients {3035, 3195}. P. marneffei has not been reported in contaminated buildings.

In humans, infection caused by Penicillium spp. due to species other than P. marneffei is rare. Actually, Penicillium species are rarely etiologically linked to documented invasive infections, although they are being increasingly recognized as potential opportunists in the immunocompromised host {926}. Penicillium spp. are identified in immunosuppressed patients, either suffering from HIV infection or on immunosuppressant medications; they are a rarely identified cause of infection in immunocompetent hosts {901}. However, P. chrysogenum is sporadically implicated in cases without clear immune suppression: such are cases of otomycoses, endophthalmitis. keratitis, endocarditis and cutaneous infections {936} and, reported in one instance, pneumonia {926}.

A case of necrotizing pneumonia caused by P. chrysogenum has been reported in a woman with a pulmonary squamous carcinoma {926}; a necrotizing lesion within an air-filled cavity was observed by a tomography scan.

A case of central nervous system infection (isolation of the mould in the cerebrospinal fluid) was reported in a patient without immunological compromise, after a severe trauma in the head 30 years before the onset of the disease, showing the possibility of a long incubation period {936, Kantarcioglu, A. S. et al, 2004}.

An endophthalmitis caused by P. chrysogenum was reported in a child after a penetrating ocular trauma with a soil contaminated object {934}. Barcus et al reported an intestinal invasion and disseminated disease associated with P. chrysogenum {901}.

Lopez-Martinez et al {904} reported a case of P. chrysogenum cutaneous penicillosis in a young man without immunological compromise.

Penicillium sp was seen microscopically and cultured from tracheal granulation tissue, in two cases of post-intubation tracheal stenosis fungal colonisation {3131}.

Experimentally, when goats were inoculated intratracheally with 30 mL of a fungal spore preparation of Penicillium chrysogenum and other fungi, showed within 6 weeks atelectatic and consolidated lung lesions {902}.

Virulence factors

No particular virulence factors are reported, except for the diphasic stages transformation of P. marneffei.

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Infectivity of P. marneffei requires the saprobic mould form to undergo a morphological change upon tissue invasion. The in vivo form of this fungus, obtained by passage to 37 °C conditions, reproduces as a fission yeast that capably evades the host immune system {3194, 3193, 3184,3185, 3195}.

Eventhough, Penicillium other than P. marneffei do not seem to have particular virulence factors, exposure to high levels of airborne Penicillum spp. seems to increase significantly the risk for lower respiratory tract illnesses in the first year of life {1462}.

Specific settings

Nosocomial infections

Penicillium spp. is often reported as the main fungus in contaminated air samples in hospitals {2080, 2409, 3009}. This fungus proliferating well in absorbent building materials {527, 3055}; it has even been suggested to use its concentration as an index of contamination {3009}. Yet Penicillium spp. is very rarely implicated in nosocomial infections and only as post-operative or iatrogenic infection in immunocompromised patients. Two cases of surgical wound infections caused by Penicillium spp. were associated to the fibreglass liners in the operating room air handling system, that were heavily contaminated by Penicillium {527}; the fibreglass was also contaminated with Aspergillus species.

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Only a handful of cases of Penicillium infections have been reported in the hospital setting. The only Penicillium species reported frequently in immusuppressed patients is P. marneffei, but it does not seem to grow on building materials: all cases seem to be community acquired. In addition, this type of infection is mostly restricted to the Far East {3035, 3195}; some “imported” cases have been reported in the United-States, Canada {3075} and Australia {3035}. Furthermore, P. marneffei cannot be mistaken with other types of Penicillium infections, because the characteristic histological presentation and diphasic mycological properties of P. marneffei are easily recognizable, and the infection occurs in late-stage immunocompromised patients {3195}.

Occupational diseases

Type III hypersensitivity pneumonites (HP) due to Penicillium are well-known in occupational setting, such as the Cheese washer's lung {3048}, Sausage maker’s lung {3167, 3211}, Woodman's lung or Sawmill worker’s lung (Sawmill lung) {3024}. Exposure in forestry and agriculture, as well as greenhouse and composting related settings, has been defined as occupational risk factors for respiratory illnesses such as HP {858}. The same is true for occupational exposure in animal care facilities {709} and for construction workers {2841,1037, 695, 3122}.

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Respiratory diseases have been often associated with lumber, sawmill and wood working environments {3003, 3024, 957, 858, 775, 1581}: in many cases, contamination of beech wood, particle board, chipboard and woodchips by different species of Penicillium have been implicated.

Penicillium pneumonitis is also prevalent in agricultural confined environments {1786, 862}, and significant exposures are particularly associated with grain unloading and handling {2500}.

Under greenhouse conditions, plantings can harbour abundant fungus growth that may become airborne, especially when agitated directly: these exposures consist mainly of Cladosporium and Penicillium spp. {1822}.

Similarly, many species of Penicillium (in conjunction with other fungi) are isolated in great numbers in compost or biowaste facilities and may represent an exposure risk to both fungal sensitisers and mVOCs and maybe toxins {2809, 1148, 855, 3092}.

Not all agro-food settings represent the same high level of exposure: for example, hop growers are exposed to lower concentrations of dust and microorganisms, yet Penicillium spp. and Alternaria alternata were the most common species: the relatively lower total counts may be partly due to antimicrobial properties of hop plants {2654}.

P. verrucosum has been reported as causing a respiratory syndrome very similar to extrinsic allergic alveolitis in workers of a cheese factory {3034}. Penicillium species are responsible for many cases of HP in bakers. Penicillium is the dominant genus in task related exposures, at least during the springtime, in bakeries {2401, 2023, 1731, 1078, 2001}.

A study has shown that Penicillium citrinum should be considered as potential occupational allergens, probably stimulating an adverse immunopathological reaction in the exposed potato processing workers {3026}.

In work stations involved with metal-working fluids (MWF), fungi like Penicillium, Aspergillus, and Cladosporium species were identified in the air, but only rarely in the MWF, and these are not as significant as endotoxins and anti bacterial IgG antibodies as indicators of occupational exposure to the microbial contaminants {229}.

Penicillium levels in air samples collected in a library and archive storage facilities indicated that they could be hazardous to workers' health {2774}.

Demolition and renovation work can be an occupational risk for construction workers, because building materials can be heavily contaminated, both overtly and hidden; this type of work warrants proper PPE when such contamination is suspected {695} or adequate confinement measures {1855}. Further research is needed concerning health effects related to bioaerosol and mycotoxin exposures of construction workers {216}.

Diagnostic tools

Histopathology

The histological presentation of a deep sited penicilliosis due to P. marneffei is typically that of a dimorphic fungal infection.

Whereas, other Penicillium invasive infections would resemble the opportunist fungal hyphal infection.

Immunodiagnosis

The Penicillium allergen extracts listed by FDA are as follow:

  • GK23 - Penicillium atramentosum
  • GK24 - Penicillium biforme
  • GK25 - Penicillium camembertii
  • GK26 - Penicillium carmino-violaceum
  • GK27 - Penicillium chrysogenum
  • GK28 - Penicillium digitatum
  • GK29 - Penicillium expansum
  • GK30 - Penicillium funiculosum
  • GK31 - Penicillium glaucum
  • GK32 - Penicillium glaucus
  • GK33 - Penicillium intricatum
  • GK34 - Penicillium italicum
  • GK35 - Penicillium janthinellum
  • GK36 - Penicillium luteum
  • GK37 - Penicillium notatum
  • GK38 - Penicillium oxalicum
  • GK39 - Penicillium roquefortii
  • GK40 - Penicillium roseo-purpureum
  • GK41 - Penicillium roseum
  • GK42 - Penicillium rubrum
  • GK43 - Penicillium spp.
  • GK44 - Penicillium vermiculatum
Test IgE IgG Antigens Other
Skin Tests X      
RAST-IgE X      
RAST-IgG   X    
ELISA-ELIFA        
Immunodiffusion        
Immunofluorescence   Experimental    
Complement fixation        
PCR     Experimental  
Other        

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Dernière modification: 

28 juillet 2016