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PENICILLIUM Mould

The U.S. Government's Occupational Safety and Health Administration [OSHA] lists the following as the health effects of Penicillium mould:  Allergen, Irritant, Hypersensitivity pneumonitis, Dermatitis.

 

Taxonomic Classifications        
 Kingdom    Fungi
         Phylum    Ascomycota
         Class    Euascomycetes
         Order    Eurotiales
         Family    Trichomaceae
         Genus    Penicillium  
Morphological structures and types of conidiophore branching in Penicillium. a. simple; b. one-stage branched; c. two-stage branched; d. three-stage branched

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Yeast

Morphological structures and types of conidiophore branching in Penicillium. a. simple; b. one-stage branched; c. two-stage branched; d. three-stage branched (Samson et al., 1984)

Colonies are usually fast growing, in shades of green, sometimes white, mostly consisting of a dense felt of conidiophores. 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-staged branched.

 

Penicillium colonies are usually fast growing, in shades of green, sometimes white, mostly consisting of a dense felt of conidiophores

Culture of Penicillium sp.

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.
Descriptions and Habitats

 Species of Penicillium are recognized by their dense brush-like spore-bearing structures.
(Source:Mycology Online)

 

Species of Penicillium are recognized by their dense brush-like spore-bearing structures. The conidiophores are simple or branched and are terminated by clusters of flask-shaped phialides. The spores (conidia) are produced in dry chains from the tips of the phialides, with the youngest spore at the base of the chain, and are nearly always green. Branching is an important feature for identifying Penicillium species. Some (top figure) are unbranched and simply bear a cluster of phialides at the top of the stipe. Others (bottom left) may have a cluster of branches, each bearing a cluster of phialides. A third type (bottom right) has branches bearing a second order of branches, bearing in turn a cluster of phialides. These three types of spore bearing systems (penicilli) are called monoverticillate, biverticillate and terverticillate respectively. Penicillium is a large and difficult genus encountered almost everywhere, and usually the most abundant genus of fungi in soils

The common occurrence of Penicillium species in food is a particular problem. Some species produce toxins and may render food inedible or even dangerous. It is a good practice to discard foods showing the development of any mould. On the other hand some species of Penicillium are beneficial to humans. Cheeses such as Roquefort, Brie, Camembert, Stilton, etc. are ripened with species of Penicillium and are quite safe to eat. The drug penicillin is produced by Penicillium chrysogenum, a commonly occurring mould in most homes

Holomorphs: Eupenicillium, Hamigera, Talaromyces, Trichocoma. Ref: Kulik 1968; Pitt 1980; Raper and Thom 1949; Ramirez, 1982; Samson, Stolk, and Hadlok 1976; Stolk and Samson, 1972, 1983.

Species

The genus Penicillium has several species. The most common ones include Penicillium chrysogenum, Penicillium citrinum, Penicillium janthinellum, Penicillium marneffei, and Penicillium purpurogenum. Identification to species level is based on colony morphology and microscopic features.

 

 

 

Some are unbranched and simply bear a cluster of phialides at the top of the stipe.

 

Others  may have a cluster of branches, each bearing a cluster of phialides.

 

A third type  has branches bearing a second order of branches, bearing in turn a cluster of phialides.

 

 

Penicillium marneffei

 

In Asia, Penicillium marneffei causes respiratory, skin, and systemic mycosis. It is the most prevalent fungus causing such diseases in South East Asia.
P. marneffei colonies become greyish-pink to brown with age and produce a diffusible brownish-red to wine red-pigment.

Culture of P. marneffei showing distinctive red diffusable pigment

Penicillium marneffei, a very pathogenic fungus, was first isolated in 1956 from the viscera of a bamboo rat (Rhizomys sinensis) in the highlands of central Vietnam, at the Pasteur Institute in Dalat, Vietnam. The isolates were sent to the Pasteur Institute in Paris for further study, and named after of Dr. Hubert Marneffe, the Director of the Institut Pasteur of Indochina.

No other animal besides humans is known to naturally acquire an infection by this fungal pathogen. Despite the apparent relationship between the fungus and the bamboo rat, exposure to these animals has not been established as a risk factor for acquiring penicilliosis. Instead, exposure to soil appears to be the critical risk factor associated with acquisition of P. marneffei infection.

The first documented case of natural human infection was discovered in 1973, in a 61-year-old US missionary suffering from Hodgkin's disease. Subsequently, additional cases were reported from Southeast Asia in the early 1980s. Late in 1996 more than 900 cases had already been diagnosed in the world, mostly from Southeast Asia. At present, the endemic areas cover all Southeast Asia where systemic infections with this organism have become very common and now is among the top three, amongst Mycobacterium tuberculosis and Cryptococcus neoformans, as the indicator disease of AIDS in Southeast Asia.

Between 1987 and 1992, there were 92 patients with documented systemic P marneffeii infection at Chiang Mai University Hospital in Northern Thailand: 86 were HIV positive. Since then, the number of cases among HIV-positive patients has increased dramatically. It is the third most common opportunistic infections in Thailand, after tuberculosis and cryptococcosis.

P. marneffei grows as a saprophytic (growing and feeding on dead or decaying organic matter) filamentous mould bearing numerous conidia, but it assumes a yeast-like morphology upon tissue invasion.

On Sabouraud's dextrose agar at 25C, colonies are fast growing, suede-like to downy, white with yellowish-green conidial heads. Colonies become greyish-pink to brown with age and produce a diffusible brownish-red to wine red-pigment. Conidiophores are hyaline, smooth-walled and bear terminal verticils of 3 to 5 metulae, each bearing 3 to 7 phialides. Conidia are globose to subglobose, 2 to 3 um in diameter, smooth-walled and are produced in basipetal succession from the phialides.

 

Phialides and conidia of P. marneffei.

Phialides and conidia of P. marneffei

On brain heart infusion (BHI) blood agar incubated at 37C, colonies are rough, bald, tan-colored and yeast-like. Microscopically, yeast-cells are spherical to ellipsoidal, 2 to 6 um in diameter, and divide by fission rather than budding. Numerous short hyphal elements are also present.

Penicillium marneffei exhibits thermal dimorphism by growing in living tissue or in culture at 37C as a yeast-like fungus or in culture at temperatures below 30C as a mould. This fungus has been isolated from bamboo rats and is endemic in Southeast Asia and the southern region of China. Over 30 cases of hyalohyphomycosis cause by P. marneffei, especially in AIDS patients have now been reported.

Health Effects

Penicillium mould are occasional causes of infection in humans and the resulting disease is known generically as penicilliosis. Penicilliosis is an infection caused by Penicillium marneffei, a dimorphic fungus endemic to Southeast Asia and the southern part of China. Persons affected by penicilliosis usually have AIDS with low CD4+ cell count of typically <100 cells/cu mm. The average CD4 count at presentation is 63.5 cells/cu mm. Penicillium marneffei infections have also been reported in non-AIDS patients with hematological malignancies and those receiving immunosuppressive therapy.

Penicillium marneffei infection, so called penicilliosis marneffei, is acquired via inhalation and results in initial pulmonary infection, followed by fungemia and dissemination of the infection . The lymphatic system, liver, spleen and bones are usually involved. Acne-like skin papules on face, trunk, and extremities are observed during the course of the disease. Penicilliosis marneffei infection is often fatal.

Patients with penicilliosis are occasionally seen outside endemic areas, but most have a history of travel to an endemic area. The most common presentation is a disseminated infection manifested by fever, skin lesions, anemia, generalized lymphadenopathy, and hepatomegaly. Localized infection such as pneumonia has also been reported.

Penicillium has been isolated from patients with keratitis, endophtalmitis, otomycosis, necrotizing esophagitis, pneumonia, endocarditis, peritonitis, and urinary tract infections. Most Penicillium infections are encountered in immunosuppressed hosts. Corneal infections are usually post-traumatic . In addition to its infectious potential, Penicillium verrucosum produces the mycotoxin ochratoxin A, which is nephrotoxic and carcinogenic. The production of the mycotoxin usually occurs in cereal grains at cold climates.

 

Clinical Features of Penicilliosis
Source: HIV InSite Knowledge Base Chapter

 

Clinical features

Percentage of cases

Fever 99%
Anemia 78%
Weight loss 76%
Skin lesions 71%
Lymphadenopathy 58%
Hepatomegaly 51%
Pulmonary disease/symptom 49%
Diarrhea 31%
Splenomegaly 16%
Oral lesions 4%
   

 

Macroscopic Features

The colonies of Penicillium other than Penicillium marneffei are rapid growing, flat, filamentous, and velvety, woolly, or cottony in texture. The colonies are initially white and become blue green, gray green, olive gray, yellow or pinkish in time. The plate reverse is usually pale to yellowish.

Penicillium marneffei is thermally dimorphic and produces filamentous, flat, radially sulcate colonies at 25°C. These colonies are bluish-gray-green at center and white at the periphery. The red, rapidly diffusing, soluble pigment observed from the reverse is very typical. At 37°C, Penicillium marneffei colonies are cream to slightly pink in color and glabrous to convoluted in texture.

Microscopic Features

For species other than Penicillium marneffei, septate hyaline hyphae (1.5 to 5 µm in diameter), simple or branched conidiophores, metulae, phialides, and conidia are observed. Metulae are secondary branches that form on conidiophores. The metulae carry the flask-shaped phialides. The organization of the phialides at the tips of the conidiophores is very typical. They form brush-like clusters which are also referred to as "penicilli". The conidia (2.5-5µm in diameter) are round, unicellular, and visualized as unbranching chains at the tips of the phialides.

In its filamentous phase, Penicillium marneffei is microscopically similar to the other Penicillium species. In its yeast phase, on the other hand, Penicillium marneffei is visualized as globose to elongated sausage-shaped cells (3 to 5 µm) that multiply by fission.

Penicillium marneffei is easily induced to produce the arthroconidial yeast-like state by subculturing the organism to an enriched medium like BHI and incubating at 35°C, in which after a week, yeast-like structures dividing by fission and hyphae with arthroconidia are formed.

Laboratory Precautions

No special precautions other than general laboratory precautions are required.

Therapy

Available data are very limited. For Penicillium chrysogenum, MICs of amphotericin B, itraconazole, ketoconazole, and voriconazole are acceptably low, while the denoted MICs for Penicillium griseofulvum are higher than those for Penicillium chrysogenum. Notably, Penicillium marneffei isolates may yield considerably high MICs for amphotericin B, flucytosine, and fluconazole and relatively low MICs for itraconazole, ketoconazole, voriconazole, and terbinafine. Further data are required to provide a more precise susceptibility profile for various Penicillium spp.

Amphotericin B, oral itraconazole, and oral fluconazole have so far been used in treatment of penicilliosis marneffei. Oral itraconazole was found to be efficient when used prophylactically against penicilliosis marneffei in patients with HIV infection.

Acknowledgment

The mycological information gathered and organized in this extensive research on the different Pathogenic Moulds was  sourced from the list of websites below:

Doctor Fungus
Mycology Online
The Mycology Net
Mycology Online
Mould-Help

Pathogenic Fungi Database

National Center for Biotechnology Info

The Institute for Genomic Research

Univ. of South Carolina School of Medicine

Clinical Mycology Online
Department of Botany, U of Toronto

The Virtual AIDS Office of Hong Kong

Wadsworth Center, NYS Dept of Health
UW-Madison Department of Botany   

HKU-Pasteur Research Centre

Occupational Safety and Health Admin [OSHA]

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