Paracoccidioides brasiliensis

Last updated

Paracoccidioides brasiliensis
Paracoccidioides brasiliensis tissue GMS.jpg
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Eukaryota
Kingdom: Fungi
Division: Ascomycota
Class: Eurotiomycetes
Order: Onygenales
Family: Ajellomycetaceae
Genus: Paracoccidioides
Species:
P. brasiliensis
Binomial name
Paracoccidioides brasiliensis
Synonyms

Zymonema brasiliensis Splend. (1912)
Coccidioides brasiliensis F.P.Almeida (1929)

Contents

Paracoccidioides brasiliensis is a dimorphic fungus and one of the two species that cause paracoccidioidomycosis (the other being Paracoccidioides lutzii). [1] [2] [3] [4] The fungus has been affiliated with the family Ajellomycetaceae (division Ascomycota) although a sexual state or teleomorph has not yet been found. [5]

History

Paracoccidioides brasiliensis was first discovered by Adolfo Lutz in 1908 in Brazil. [6] Although Lutz did not suggest a name for the disease caused by this fungus, he made note of structures he called "pseudococcidica" together with mycelium in cultures grown at 25 °C. [6] In 1912, Alfonse Splendore [7] proposed the name Zymonema brasiliense and described the features of the fungus in culture. [6] Finally in 1930, Floriano de Almeida created the genus Paracoccidioides to accommodate the species, noting its distinction from Coccidioides immitis . [6]

Physiology

Paracoccidioides brasiliensis is a nonphotosynthetic eukaryote with a rigid cell wall and organelles very similar to those of higher eukaryotes. [3] [8] Being a dimorphic fungus, it has the ability to grow an oval yeast-like form at 37 °C and an elongated mycelial form produced at room temperature. [9] The mycelial and yeast phases differ in their morphology, biochemistry, and ultrastructure. [8] The yeast form contains large amounts of α-(1,3)-linked glucan. [10] [ page needed ] [11] The chitin content of the mycelial form is greater than that of the yeast form, but the lipid content of both phases is comparable. [10] [ page needed ]

The yeast reproduces by asexual budding, where daughter cells are borne asynchronously at multiple, random positions across the cell surface. Buds begin by layers of cell wall increasing in optical density at a point that eventually gives rise to the daughter cell. [3] Once the bud has expanded, a cleavage plane develops between the nascent cell and the mother cell. Following dehiscence, the bud scar disappears. [8] In tissue, budding occurs inside the granulomatous center of the disease lesion, as visualized by hematoxylin and eosin (H&E) staining of histologic sections. [10] Nonbudding cells measure 5–15 µm in diameter, whereas those with multiple spherical buds measure from 10–20 µm in diameter. [10] In electron microscopy, cells with multiple buds have been found to have peripherally located nuclei and cytoplasm surrounding a large central vacuole. [12] In the tissue form of P. brasiliensis, yeast cells are larger with thinner walls and a narrower bud base than those of the related dimorphic fungus, Blastomyces dermatitidis . [10] [ page needed ] The yeast-like form of P. brasiliensis contains multiple nuclei, a porous two-layered nuclear membrane, and a thick cell wall rich in fibers, whereas the mycelial phase has thinner cell walls with a thin, electron-dense outer layer. [8]

Dimorphism

The mycelial form of P. brasiliensis can be converted to the yeast form in vitro by growth on brain heart infusion agar or blood-glucose-cysteine agar when incubated for 10–20 days at 37 °C. [10] Under these conditions, hyphal cells either die or convert to transitional forms measuring 6–30 µm in diameter, which ultimately detach or remain on the hyphal cells, yielding buds. [10] New buds develop mesosomes and become multinucleated. [10] In contrast, yeast-like cultures can be converted to the mycelial form by reducing the incubation temperature from 37 to 25 °C. [13] Initially, nutritional requirements of both the yeast and mycelial phases of P. brasiliensis were thought to be identical; [14] however, later studies demonstrated the yeast form to be auxotrophic, requiring exogenous sulfur-containing amino acids including cysteine and methionine for growth. [15]

Ecology

Although the habitat of P. brasiliensis remains unknown, it is commonly associated with soils in which coffee is cultivated. [5] [16] [17] It has also been associated with the nine-banded armadillo, Dasypus novemcinctus. [18] The disease caused by P. brasiliensis is mostly geographically restricted to Latin American countries such as Brazil, Colombia, and Venezuela, with the greatest number of cases seen in Brazil. [10] The endemic areas are characterized by hot, humid summers, dry temperate winters, average annual temperatures between 17 and 23 °C, and annual rainfall between 500 and 800 mm. [19] However, the precise ecology regularities of the fungus remain elusive, and P. brasiliensis has rarely been encountered in nature outside the human host. [3] One such rare example of environmental isolation was reported in 1971 by Maria B.de Albornoz and colleagues who isolated P. brasiliensis from samples of rural soil collected in Paracotos in the state of Miranda, Venezuela. [20] In in vitro studies, the fungus has been shown to grow when inoculated into soil and sterile horse or cow excrement. [21] The mycelial phase has also been shown to survive longer than the yeast phase in acidic soil. [22] Despite a sexual state not having been documented, molecular investigations suggest the existence of recombining populations of P. brasiliensis, potentially by means of an undiscovered sexual state. [23]

The existence of a sexual cycle in P. brasiliensis, is supported by both molecular and morphological data. [24] A comparative genome analysis with other well-studied fungi demonstrated the presence of sex-related genes in both the yeast and mycelial phases of P. brasiliensis. [24] Also crosses of isolates of different mating types led to the formation of young ascocarps (sexual structures) with constricted coiled hyphae related to the initial stage of mating. [24]

Epidemiology

Paracoccidioides brasiliensis causes a disease known as paracoccidioidomycosis characterized by slow, progressive granulomatous changes in the head mucosa, notably the nose and sinuses or the skin. Uncommonly, the disease affects the lymphatic system, the central nervous system, the gastrointestinal tract, or the skeletal system. [10] Due to the high proportion of cases affecting the oral mucosa, these tissues were originally thought to be the primary route of entry of fungus. [3] However, strong evidence now indicates the respiratory tract is the chief point of entry [10] and P. brasiliensis lung lesions occur in nearly a third of progressive cases. [25] The disease is not contagious. [10] Paracoccidioidomycosis is more frequently seen in adult males than females. [10] [26] The hormone estrogen is thought to inhibit the transformation of the mycelial to the yeast form, as supported by in vitro experimental data, and this factor may account for the relative resistance of women to infection. [27]

Detection and surveillance

A number of serologic tests have been employed for the diagnosis of paracoccidioidomycosis. [10] Double diffusion in agar gel and complement fixation test, are amongst the most commonly used tests in serodiagnosis. [10] Culture extracts of the yeast or mycelia are exploited to produce effective, quick, and reproducible antigens. [10] [28] A study reported detection of 43 kD antigen in pooled sera of affected individuals, which might provide a basis for the development of a diagnostic test. [29] Tests targeting the presence of serum antibodies to P. brasiliensis simultaneously detect both active and historical infections and cannot discriminate active infection. The evaluation of populations in endemic zones has shown roughly equal rates of seroconversion between men and women, suggesting equal rates of exposure, despite the strong male predominance shown by the clinical disease. [10]

Clinical manifestations

Paracoccidioides brasiliensis causes mucous membrane ulceration of the mouth and nose with spread through the lymphatic system. A hypothesized portal of entry for the fungus to the body is through the periodontal membrane. [30] [31] The route of infection is assumed to be inhalation following which the infective propagule gives rise to the distinctive multipolar budding yeast forms in the lung resembling a "ship's wheel" seen in histological sections. [9] [32] Both immunologically normal and compromised people are at risk for infection. [9] The lungs, lymph nodes, and mucous membrane of the mouth are the most frequently infected tissues. [10] The pathological features of paracoccidioidomycosis are similar to those seen in coccidioidomycosis and blastomycosis. [33] However, in the former, the lesions first appear in the lymphoid tissue and then extend to mucous membranes, [33] producing localized to diffusive tissue necrosis of the lymph nodes. [33] The typically extensive involvement of lymphoid tissue and the limited occurrence of the gastrointestinal tract, bone and prostate set the clinical picture of paracoccidioidomycosis apart from that of blastomycosis. [10] [33]

Related Research Articles

<span class="mw-page-title-main">Ascomycota</span> Division or phylum of fungi

Ascomycota is a phylum of the kingdom Fungi that, together with the Basidiomycota, forms the subkingdom Dikarya. Its members are commonly known as the sac fungi or ascomycetes. It is the largest phylum of Fungi, with over 64,000 species. The defining feature of this fungal group is the "ascus", a microscopic sexual structure in which nonmotile spores, called ascospores, are formed. However, some species of Ascomycota are asexual and thus do not form asci or ascospores. Familiar examples of sac fungi include morels, truffles, brewers' and bakers' yeast, dead man's fingers, and cup fungi. The fungal symbionts in the majority of lichens such as Cladonia belong to the Ascomycota.

<i>Talaromyces marneffei</i> Species of fungus

Talaromyces marneffei, formerly called Penicillium marneffei, was identified in 1956. The organism is endemic to southeast Asia where it is an important cause of opportunistic infections in those with HIV/AIDS-related immunodeficiency. Incidence of T. marneffei infections has increased due to a rise in HIV infection rates in the region.

<i>Cryptococcus</i> Genus of fungi

Cryptococcus is a genus of fungi in the family Cryptococcaceae that includes both yeasts and filamentous species. The filamentous, sexual forms or teleomorphs were formerly classified in the genus Filobasidiella, while Cryptococcus was reserved for the yeasts. Most yeast species formerly referred to Cryptococcus have now been placed in different genera. The name Cryptococcus comes from the Greek for "hidden sphere". Some Cryptococcus species cause a disease called cryptococcosis.

<i>Candida</i> (fungus) Genus of ascomycete fungi

Candida is a genus of yeasts. It is the most common cause of fungal infections worldwide and the largest genus of medically important yeast.

<span class="mw-page-title-main">Blastomycosis</span> Medical condition

Blastomycosis, also known as Gilchrist's disease, is a fungal infection, typically of the lungs, which can spread to brain, stomach, intestine and skin, where it appears as crusting purplish warty plaques with a roundish bumpy edge and central depression. Only about half of people with the disease have symptoms, which can include fever, cough, night sweats, muscle pains, weight loss, chest pain, and feeling tired. Symptoms usually develop between three weeks and three months after breathing in the spores. In 25% to 40% of cases, the infection also spreads to other parts of the body, such as the skin, bones or central nervous system. Although blastomycosis is especially dangerous for those with weak immune systems, most people diagnosed with blastomycosis have healthy immune systems.

<i>Malassezia</i> Genus of fungi

Malassezia is a genus of fungi. It is the sole genus in family Malasseziaceae, which is the only family in order Malasseziales, itself the single member of class Malasseziomycetes. Malassezia species are naturally found on the skin surfaces of many animals, including humans. In occasional opportunistic infections, some species can cause hypopigmentation or hyperpigmentation on the trunk and other locations in humans. Allergy tests for these fungi are available. It is believed French revolutionary Jean-Paul Marat suffered from a fungal infection from Malassezia restricta, which lead to his frequent bathing in a medicinal substance.

Candida parapsilosis is a fungal species of yeast that has become a significant cause of sepsis and of wound and tissue infections in immunocompromised people. Unlike Candida albicans and Candida tropicalis, C. parapsilosis is not an obligate human pathogen, having been isolated from nonhuman sources such as domestic animals, insects and soil. C. parapsilosis is also a normal human commensal and it is one of the fungi most frequently isolated from human hands. There are several risk factors that can contribute to C. parapsilosis colonization. Immunocompromised individuals and surgical patients, particularly those undergoing surgery of the gastrointestinal tract, are at high risk for infection with C. parapsilosis. There is currently no consensus on the treatment of invasive candidiasis caused by C. parapsilosis, although the therapeutic approach typically includes the removal of foreign bodies such as implanted prostheses and the administration of systemic antifungal therapy. Amphotericin B and Fluconazole are often used in the treatment of C. parapsilosis infection.

<span class="mw-page-title-main">Paracoccidioidomycosis</span> Medical condition

Paracoccidioidomycosis (PCM), also known as South American blastomycosis, is a fungal infection that can occur as a mouth and skin type, lymphangitic type, multi-organ involvement type (particularly lungs), or mixed type. If there are mouth ulcers or skin lesions, the disease is likely to be widespread. There may be no symptoms, or it may present with fever, sepsis, weight loss, large glands, or a large liver and spleen.

<i>Sporothrix schenckii</i> Species of fungus

Sporothrix schenckii, a fungus that can be found worldwide in the environment, is named for medical student Benjamin Schenck, who in 1896 was the first to isolate it from a human specimen. The species is present in soil as well as in and on living and decomposing plant material such as peat moss. It can infect humans as well as animals and is the causative agent of sporotrichosis, commonly known as "rose handler's disease." The most common route of infection is the introduction of spores to the body through a cut or puncture wound in the skin. Infection commonly occurs in otherwise healthy individuals but is rarely life-threatening and can be treated with antifungals. In the environment it is found growing as filamentous hyphae. In host tissue it is found as a yeast. The transition between the hyphal and yeast forms is temperature dependent making S. schenckii a thermally dimorphic fungus.

<i>Histoplasma capsulatum</i> Species of fungus

Histoplasma capsulatum is a species of dimorphic fungus. Its sexual form is called Ajellomyces capsulatus. It can cause pulmonary and disseminated histoplasmosis.

<i>Blastomyces dermatitidis</i> Species of fungus

Blastomyces dermatitidis is a dimorphic fungus that causes blastomycosis, an invasive and often serious fungal infection found occasionally in humans and other animals. It lives in soil and wet, decaying wood, often in an area close to a waterway such as a lake, river or stream. Indoor growth may also occur, for example, in accumulated debris in damp sheds or shacks. The fungus is endemic to parts of eastern North America, particularly boreal northern Ontario, southeastern Manitoba, Quebec south of the St. Lawrence River, parts of the U.S. Appalachian mountains and interconnected eastern mountain chains, the west bank of Lake Michigan, the state of Wisconsin, and the entire Mississippi Valley including the valleys of some major tributaries such as the Ohio River. In addition, it occurs rarely in Africa both north and south of the Sahara Desert, as well as in the Arabian Peninsula and the Indian subcontinent. Though it has never been directly observed growing in nature, it is thought to grow there as a cottony white mold, similar to the growth seen in artificial culture at 25 °C (77 °F). In an infected human or animal, however, it converts in growth form and becomes a large-celled budding yeast. Blastomycosis is generally readily treatable with systemic antifungal drugs once it is correctly diagnosed; however, delayed diagnosis is very common except in highly endemic areas.

Lacazia is a genus of fungi containing the single species Lacazia loboi, which is responsible for Lobo's disease. It is a member of the order Onygenales.

<span class="mw-page-title-main">Dimorphic fungus</span> Fungi that can exist as mold or yeast

Dimorphic fungi are fungi that can exist in the form of both mold and yeast. This is usually brought about by change in temperature and the fungi are also described as thermally dimorphic fungi. An example is Talaromyces marneffei, a human pathogen that grows as a mold at room temperature, and as a yeast at human body temperature.

<i>Microsporum audouinii</i> Species of fungus

Microsporum audouinii is an anthropophilic fungus in the genus Microsporum. It is a type of dermatophyte that colonizes keratinized tissues causing infection. The fungus is characterized by its spindle-shaped macroconidia, clavate microconidia as well as its pitted or spiny external walls.

<i>Fonsecaea pedrosoi</i> Species of fungus

Fonsecaea pedrosoi is a fungal species in the family Herpotrichiellaceae, and the major causative agent of chromoblastomycosis. This species is commonly found in tropical and sub-tropical regions, especially in South America, where it grows as a soil saprotroph. Farming activities in the endemic zone are a risk factor for the development of chromoblastomycosis.

Histoplasma duboisii is a saprotrophic fungus responsible for the invasive infection known as African histoplasmosis. This species is a close relative of Histoplasma capsulatum, the agent of classical histoplasmosis, and the two occur in similar habitats. Histoplasma duboisii is restricted to continental Africa and Madagascar, although scattered reports have arisen from other places usually in individuals with an African travel history. Like, H. capsulatum, H. duboisii is dimorphic – growing as a filamentous fungus at ambient temperature and a yeast at body temperature. It differs morphologically from H. capsulatum by the typical production of a large-celled yeast form. Both agents cause similar forms of disease, although H. duboisii predominantly causes cutaneous and subcutaneous disease in humans and non-human primates. The agent responds to many antifungal drug therapies used to treat serious fungal diseases.

<i>Cladophialophora carrionii</i> Species of fungus

Cladophialophora carrionii is a melanized fungus in the genus Cladophialophora that is associated with decaying plant material like cacti and wood. It is one of the most frequent species of Cladophialophora implicated in human disease. Cladophialophora carrionii is a causative agent of chromoblastomycosis, a subcutaneous infection that occurs in sub-tropical areas such as Madagascar, Australia and northwestern Venezuela. Transmission occurs through traumatic implantation of plant material colonized by C. carrionii, mainly infecting rural workers. When C. carrionii infects its host, it transforms from a mycelial state to a muriform state to better tolerate the extreme conditions in the host's body.

<i>Candida tropicalis</i> Species of fungus

Candida tropicalis is a species of yeast in the genus Candida. It is a common pathogen in neutropenic hosts, in whom it may spread through the bloodstream to peripheral organs. For invasive disease, treatments include amphotericin B, echinocandins, or extended-spectrum triazole antifungals.

Arthrographis kalrae is an ascomycetous fungus responsible for human nail infections described in 1938 by Cochet as A. langeronii. A. kalrae is considered a weak pathogen of animals including human restricted to the outermost keratinized layers of tissue. Infections caused by this species are normally responsive to commonly used antifungal drugs with only very rare exceptions.

<i>Paracoccidioides lutzii</i> Species of fungus

Paracoccidioides lutzii is a dimorphic fungus that is one of the causal agents of paracoccidioidomycosis, together with Paracoccidioides brasiliensis. Unlike P. brasiliensis, which is found throughout Central and South America, P. lutzii is found only in Brazil and Ecuador. It is less virulent than P. brasiliensis.

References

  1. Martinez, Roberto; Moretti, Maria Luiza; Camargo, Zoilo Pires de; Khoury, Zarifa; Durlacher, Rui Rafael; Hahn, Rosane; Cavalcante, Ricardo de Souza; Pereira, Ricardo Mendes; Silva-Vergara, Mario León (September 2017). "Brazilian guidelines for the clinical management of paracoccidioidomycosis". Revista da Sociedade Brasileira de Medicina Tropical. 50 (5): 715–740. doi: 10.1590/0037-8682-0230-2017 . hdl: 11449/163455 . ISSN   0037-8682. PMID   28746570.
  2. Ryan, KJ (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. p. 683. ISBN   0-8385-8529-9.
  3. 1 2 3 4 5 Pan American Health Organization (October 1971). Paracoccidioidomycosis; Proceedings of the first Pan American symposium (1st ed.). Medellín, Colombia: Washington Pan American Health Organization. p. 325. Scientific Publication No. 254.
  4. Brummer E, Castaneda E, Restrepo A (1993). "Paracoccidioidomycosis: an update". Clin. Microbiol. Rev. 6 (2): 89–117. doi:10.1128/cmr.6.2.89. PMC   358272 . PMID   8472249.
  5. 1 2 Bagagli E, Theodoro RC, Bosco SM, et al. (2008). "Paracoccidioides brasiliensis: phylogenetic and ecological aspects". Mycopathologia. 165 (4–5): 197–207. doi: 10.1007/s11046-007-9050-7 . PMID   18777629.
  6. 1 2 3 4 Lacaz, Carlos S. (1994). "Historical evolution of the knowledge on paracoccidioidomycosis and its etiologic agent, Paracoccidioides brasiliensis". In Franco, Marcello; Lacaz, Carlos da Silva; Restrepo-Moreno, Angela; Del Negro, Gildo (eds.). Paracoccidioidomycosis. Boca Raton, Florida: CRC Press. pp. 1–11. ISBN   978-1-351-07532-9.
  7. "Alfonso Splendore". Whonamedit? - A dictionary of medical eponyms. Retrieved 24 January 2024.
  8. 1 2 3 4 Carbonell, Luis M (1963). "Ultrastructure of Paracoccidiodes brasiliensis". Mycopathologia et Mycologia Applicata. 19 (3): 184–204. doi:10.1007/bf02051247. ISSN   0027-5530. PMID   14045074.
  9. 1 2 3 Reiss, E (2011). Fundamental Medical Mycology. Hoboken, New Jersey: Wiley-Blackwell. p. 624. ISBN   9780470177914.
  10. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Kwon-Chung, K.J; Bennett, John E (1992). Medical Mycology. Philadelphia: Philadelphia: Lea & Febiger. ISBN   0812114639.
  11. Kanetsuna, F; et al. (1969). "Cell wall composition of the yeast and mycelial forms of Paracoccidioides brasiliensis". J. Bacteriol. 97 (3): 1036–1041. doi:10.1128/jb.97.3.1036-1041.1969. PMC   249811 . PMID   5776517.
  12. Furtado, J.S; Freymuller E. (1967). "The structure and reproduction of Paracoccidioides brasiliensis in human tissue". Sabouraudia. 5 (3): 226–229. doi:10.1080/00362176785190431. PMID   6036228.
  13. Ramirez-Martinez, J.R (1971). "Paracoccidioides brasiliensis: Conversion of yeast-like forms into mycelia in submerged culture". J. Bacteriol. 105 (2): 523–526. doi:10.1128/jb.105.2.523-526.1971. PMC   248414 . PMID   5541529.
  14. Gilardi, G.L (1965). "Nutrition of systematic and subcutaneous pathogenic fungi". Bacteriol. Rev. 29 (3): 406–424. doi:10.1128/br.29.3.406-424.1965. PMC   441289 . PMID   5318450.
  15. Paris, S; Duran-Gonzalez S. (1985). "Nutritional studies on Paracoccidioides brasiliensis: the role of organic sulfur in dimorphism". Sabouraudia. 23 (2): 85–92. doi:10.1080/00362178585380151. PMID   4012515.
  16. Flannigan, Brian (2001). Microorganisms in Home and Indoor Work Environments: Diversity, Health Impacts, Investigation and Control. New York: Taylor & Francis. p. 479. ISBN   9780203302934.
  17. Terçarioli GR, Bagagli E, Reis GC, et al. (2007). "Ecological study of Paracoccidioides brasiliensis in soil: growth ability, conidia production and molecular detection". BMC Microbiol. 7: 92–99. doi: 10.1186/1471-2180-7-92 . PMC   2180180 . PMID   17953742.
  18. Bagagli, Eduardo; Bosco, Sandra M.G.; Theodoro, Raquel Cordeiro; Franco, Marcello (September 2006). "Phylogenetic and evolutionary aspects of Paracoccidioides brasiliensis reveal a long coexistence with animal hosts that explain several biological features of the pathogen". Infection, Genetics and Evolution. 6 (5): 344–351. doi:10.1016/j.meegid.2005.12.002. PMID   16473563.
  19. Borelli, D (1969). "Reservareas de algunos agentes de micosis". Med. Cutan. Iber. Lat. Am. 3: 367–370.
  20. Albornoz, M; Albornoz (1971). "Estudio de la sensibilidad especifica en residents de un area endemica a la paracoccidiodomycosis en Venezuela". Mycopathologia. 45 (2): 65–75. doi:10.1007/bf02059246. PMID   5129432. S2CID   9245772.
  21. Borelli, D (1961). "Hipotesis sobre ecologia de Paracoccidioides". Derm. Venez. 3: 130–132.
  22. Restrepo, M; et al. (1969). "Effect of hydrogen ion concentration and of temperature on the growth of Paracoccidioides brasiliensis in soil extract". Sabouraudia. 7 (3): 207–215. doi:10.1080/00362177085190371. PMID   5385156.
  23. Matute, D. R.; el al. (24 August 2005). "Cryptic Speciation and Recombination in the Fungus Paracoccidioides brasiliensis as Revealed by Gene Genealogies". Molecular Biology and Evolution. 23 (1): 65–73. doi: 10.1093/molbev/msj008 . PMID   16151188.
  24. 1 2 3 Teixeira Mde M, Theodoro RC, Derengowski Lda S, Nicola AM, Bagagli E, Felipe MS. Molecular and morphological data support the existence of a sexual cycle in species of the genus Paracoccidioides. Eukaryot Cell. 2013 Mar;12(3):380-9. doi: 10.1128/EC.05052-11. Epub 2012 Nov 2. PMID 23125354; PMCID: PMC3629771
  25. Londero, A.T; Ramos C.D (1972). "Paracoccidioidomycosis: a clinical and mycologic study in forty one cases observed in Santa Maria, RS, Brazil". Am. J. Med. 52 (6): 771–775. doi:10.1016/0002-9343(72)90083-6. PMID   5030174.
  26. Restrepo, M; Restrepo A (1970). "Paracoccidiomycosis (South American blastomycosis): a study of 39 cases observed in Medellin, Colombia". Am. J. Trop. Med. Hyg. 19 (1): 68–76. doi:10.4269/ajtmh.1970.19.68. PMID   4984585.
  27. Restrepo, M; et al. (1984). "Estrogens inhibit mycelial to yeast transformation in the fungus Paracoccidioides brasiliensis: implications for resistance of females to paracoccidioidomycosis". Infect. Immun. 46 (2): 346–353. doi:10.1128/iai.46.2.346-353.1984. PMC   261537 . PMID   6500694.
  28. Blumer, S.O; Jalbert M (1984). "Rapid and reliable method for production of a specific Paracoccidioides brasiliensis immunodiffucsion test antigen". J. Clin. Microbiol. 19 (3): 404–407. doi:10.1128/jcm.19.3.404-407.1984. PMC   271074 . PMID   6425358.
  29. Mendes-Giannini, M.J.S; et al. (1989). "Detection of the 43,000-molecular-weight glycoprotein in sera of patients with paracoccidioidomycosis". J. Clin. Microbiol. 27 (12): 2842–2845. doi:10.1128/jcm.27.12.2842-2845.1989. PMC   267138 . PMID   2592544.
  30. Smith J M (1969). "Mycoses of the alimentary tract". Gut. 10 (12): 1035–1040. doi:10.1136/gut.10.12.1035. PMC   1553013 . PMID   4904223.
  31. García AM, Hernández O, Aristizabal BH, et al. (2010). "Gene expression analysis of Paracoccidioides brasiliensis transition from conidium to yeast cell". Med. Mycol. 48 (1): 147–154. doi: 10.3109/13693780903055673 . PMID   19568977. S2CID   22151171.
  32. Restrepo A, McEwen JG, Castañeda E (2001). "The habitat of Paracoccidioides brasiliensis: how far from solving the riddle?". Med. Mycol. 39 (3): 233–41. doi:10.1080/714031028. PMID   11446526.
  33. 1 2 3 4 Rippon, John (1982). Medical mycology : the pathogenic fungi and the pathogenic actinomycetes (2nd ed.). Philadelphia: Saunders. ISBN   0721675867.