Abstract
Paracoccidioides brasiliensis is a dimorphic fungus, a causative agent of paracoccidioidomycosis, one of the most frequent systemic mycoses that affect the rural population in Latin America, only geographical region in which this fungus is to be found. In this work, we discuss matters related to (a) cell wall studies based on the cloning and analysis of genes involved in the synthesis of cell wall components, and their possible roles in virulence and dimorphism in P. brasiliensis, (b) molecular taxonomy and the molecular classification of P. brasiliensis as an Ascomycete belonging in the Order Onygenales, (c) phylogeny of P. brasiliensis and the possible existence of cryptic species within the genus Paracoccidioides, and (d) new experimental antifungal drugs such as azasterols or sterol hydrazones, compounds that affect the activity of Δ24(28) sterol methyl reductase (SMR) and/or Δ(24)-sterol methyl transferase (SMT), and (e) specific primers for the molecular detection of P. brasiliensis in vitro and in clinical samples.
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References
Berman J. Morphogenesis and cell cycle progression in Candida albicans. Curr Opin Microbiol 2006;9:595–601.
Momany M. Growth control and polarization. Med Mycol 2005;43(Suppl 1):S23–5.
San-Blas G, Niño-Vega G, Iturriaga T. Paracoccidioides brasiliensis and paracoccidioidomycosis: molecular approaches to morphogenesis, diagnosis, epidemiology, taxonomy and genetics. Med Mycol 2002;40:225–42.
Wanke B, Londero AT. Epidemiology and paracoccidioidomycosis infection. In: Franco M, Lacaz CS, Restrepo-Moreno A, Del Negro G, editors. Paracoccidioidomycosis. Boca Raton: CRC Press; 1994. p. 109–20.
Shikanai-Yasuda MA, Queiroz-Telles F, Mendes RP, Colombo AL, Moretti ML. Consenso em paracoccidioidomicose. Rev Soc Bras Med Trop 2006;39:297–310.
San-Blas G, Niño-Vega G. Morphogenesis of agents of endemic mycoses. In: San-Blas G, Calderone R, editors. Pathogenic fungi: structural biology and taxonomy, chapter 5. Caister Wymondham, Norfolk: Academic Press; 2004. p. 167–220.
Klis FM, Mol P, Hellingwerf K, Brul S. Dynamics of cell wall structure in Saccharomyces cerevisiae. FEMS Microbiol Rev 2002;26:239–56.
Lesage G, Bussey H. Cell wall assembly in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 2006;70:317–47.
Bartnicki-Garcia S. Cell wall chemistry, morphogenesis and␣taxonomy of fungi. Annu Rev Microbiol 1968;22: 87–108.
Roncero C. The genetic complexity of chitin synthesis in fungi. Curr Genet 2002;41:367–78.
Munro CA, Gow NAR. Chitin synthesis in human pathogenic fungi. Med Mycol 2001;39:41–53.
Odds FC, Brown AJP, Gow NAR. Antifungal agents: mechanisms of action. Trends Microbiol 2003;11:272–9.
Kanetsuna F, Carbonell LM, Moreno RE, Rodriguez J. Cell wall composition of the yeast and mycelial forms of Paracoccidioides brasiliensis. J Bacteriol 1969;97:1036–41.
Kanetsuna F, Carbonell LM, Azuma I, Yamamura Y. Biochemical studies on the thermal dimorphism of Paracoccidioides brasiliensis. J Bacteriol 1972;110:208–18.
San-Blas G, San-Blas F, Serrano LE. Host-parasite relationships in the yeastlike form of Paracoccidioides brasiliensis strain IVIC Pb9. Infect Inmun 1977;15:343–6.
Manners DJ, Meyer MT. The molecular structures of some glucans from the cell walls of Schizosaccharomyces pombe. Carbohydr Res 1977;57:189–203.
Zonneveld BJM. Morphogenesis in Aspergillus nidulans. The significance of a α-1,3-glucan of the cell wall and α-1,3-glucanase for cleistothecium development. Biochim Biophys Acta 1972;273:174–187.
Horisberger M, Lewis BA, Smith F. Structure of a (1–3)-alpha-d-glucan (pseudonigeran) of Aspergillus niger NNRL 326 cell wall. Carbohydr Res 1972;23:183–8.
Fontaine T, Simenel C, Dubreucq G, Adam O, Delepierre M, Lemoine J, et al. Molecular organization of the alkali-insoluble fraction of Aspergillus fumigatus cell wall. J Biol Chem 2000;275:27594–607.
Reese AJ, Doering TL. Cell wall alpha-1,3-glucan is required to anchor the Cryptococcus neoformans capsule. Mol Microbiol 2003;50:1401–9.
James PG, Cherniak R, Jones RG, Stortz CA, Reiss E. Cell-wall glucans of Cryptococcus neoformans Cap 67. Carbohydr Res 1990;198:23–38.
Hogan LH, Klein BS. Altered expression of surface alpha-1,3-glucan in genetically related strains of Blastomyces dermatitidis that differ in virulence. Infect Inmmun 1994;62:3543–6.
Grün CH, Hochstenbach F, Humbel BM, Verkleij AJ, Sietsma JH, Klis FM, et al. The structure of cell wall α-glucan from fission yeast. Glycobiology 2005;15:245–57.
Hochstenbach F, Klis FM, van den Ende H, van Donselaar E, Peters PJ, Klausner RD. Identification of a putative alpha-glucan synthase essential for cell wall construction and morphogenesis in fission yeast. Proc Natl Acad Sci USA 1998;95:9161–6.
Katayama S, Hirata D, Arellano M, Pérez P, Toda T. Fission yeast α-glucan synthase Mok1 requires the actin␣cytoskeleton to localize the sites of growth and plays an essential role in cell morphogenesis downstream of␣protein kinase C function. J Cell Biol 1999;144:1173–86.
Damveld RA, van Kuyk PA, Arentshorst M, Klis FM, van den Hondel CAMJJ, Ram AFJ. Expression of agsA, one of five 1,3-α-d-glucan synthase—encoding genes in Aspergillus niger, is induced in response to cell wall stress. Fungal Genet Biol 2005;42:165–77.
Henrissat B. A classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 1991;280:309–16.
Ruiz-Herrera J, González-Prieto JM, Ruiz-Medrano R. Evolution and phylogenetic relationships of chitin synthase from yeast and fungi. FEMS Yeast Res 2002;1:247–56.
Niño-Vega GA, Carrero L, San-Blas G. Isolation of the CHS4 gene of Paracoccidioides brasiliensis and its accomodation in a new class of chitin synthases. Med Mycol 2004;42:51–7.
Mandel MA, Galgiani JN, Kroken S, Orbach MJ. Coccidioides posadasii contains single chitin synthase genes corresponding to classes I to VII. Fungal Genet Biol 2006;43:775–88.
Niño-Vega GA, Buurman ET, Gooday GW, San-Blas G, Gow NAR. Molecular cloning and sequencing of a chitin synthase gene (CHS2) of Paracoccidioides brasiliensis. Yeast 1998;14:181–7.
Niño-Vega GA, Munro CA, San-Blas G, Gooday GW, Gow NAR. Differential expression of chitin synthase genes during temperature-induced dimorphic transitions in Paracoccidioides brasiliensis. Med Mycol 2000;38:31–9.
Tomazett PK, Cruz AH, Bonfim SM, Soares CM, Pereira M. The cell wall of Paracoccidioides brasiliensis: insights from its transcriptome. Genetics Mol Res 2005;4: 309–325.
San Blas G, San Blas F. Biochemistry of Paracoccidioides brasiliensis dimorphism. In: Franco M, Lacaz C, Restrepo-Moreno A, Del Negro, A, editors. Paracoccidioidomycosis. Boca Raton, Florida: CRC Press; 1994. p. 49–66.
Leclerc MC, Phillipe H, Guého E. Phylogeny of dermatophytes and dimorphic fungi based on large subunit ribosomal RNA sequence comparisons. J Med Vet Mycol 1994;32:331–41.
Niño-Vega G, Pérez-Silva C, San-Blas G. The actin gene in Paracoccidioides brasiliensis: organization, expression and phylogenetic analyses. Mycol Res 2007;111:363–9.
Kwon-Chung KJ. Emmonsiella capsulata: perfect state of Histoplasma capsulatum. Science 1972;177:368–9.
Torres-Guzmán JC, Xoconostle-Cazares B, Guevara- Olvera L, Ortiz L, San-Blas G, Domínguez A, et al. Comparison of fungal ornithine decarboxylases. Curr Microbiol 1996;33:390–2.
Niño-Vega GA, Sorais F, Calcagno AM, Ruiz-Herrera J, Martínez-Espinoza AD, San-Blas G. Cloning and expression analysis of the ornithine decarboxylase gene (PbrODC) of the pathogenic fungus Paracoccidioides brasiliensis. Yeast 2004;21:211–8.
Bowman BH, White TJ, Taylor JW. Human pathogenic fungi and their close nonpathogenic relatives. Mol Phylogenet Evol 1996;6:89–96.
Peterson SW, Sigler L. Molecular genetic variation in Emmonsia crescens and Emmonsia parva, etiologic agents of adiaspiromycosis, and their phylogenetic relationship to Blastomyces dermatitidis (Ajellomyces dermatitidis) and other systemic fungal pathogens. J Clin Microbiol 1998;36:2918–25.
Bialek R, Ibricevic A, Aepinus C, Najvar LK, Fothergill AW, Knobloch J, et al. Detection of Paracoccidioides brasiliensis in tissue samples by a nested PCR assay. J Clin Microbiol 2000;38:2940–2.
Leal JA, Prieto A, Ahrazem O, Pereyra T, Bernabé M. Cell wall polysaccharides: Characters for fungal taxonomy and evolution. Rec Res Develop Microbiol 2001;5:235–48.
Prieto A, Ahrazem O, Bernabé M, Leal JA. Polysaccharides F1SS. Taxonomic and evolutionary characters for ascomycetes. In: San-Blas G, Calderone R, editors. Pathogenic fungi: structural biology and taxonomy, chapter 10. Wymondham, Norfolk: Caister Academic Press; 2004. p.␣␣319–60.
Prieto A, Ahrazem O, San-Blas G, Leal JA, Jiménez-Barbero J, Bernabé M. Structural differences between the alkali-extracted water-soluble cell wall polysaccharides from mycelial and yeast phases of the pathogenic dimorphic fungus Paracoccidioides brasiliensis. Glycobiology 2003;13:743–7.
San-Blas G, Prieto A, Bernabé M, Ahrazem O, Moreno B, Leal JA. α-Galf 1→6-α-mannopyranoside side chains in Paracoccidioides brasiliensis cell wall are shared by members of the Onygenales, but not by galactomannans of other fungal genera. Med Mycol 2005;43:153–9.
Fisher MC, Koenig GL, White TJ, Taylor JW. Molecular and phenotypic description of Coccidioides posadasii sp. nov., previously recognized as the non-Californian population of Coccidioides immitis. Mycologia 2002;94:73–84.
Taylor JW, Fisher MC. Fungal multilocus sequence typing—it’s not just for bacteria. Curr Op Microbiol 2003;6:351–6.
Kasuga T, White TJ, Koenig G, McEwen J, Restrepo A, Castaneda E, et al. Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol 2003;12:3383–401.
Calcagno AM, Niño-Vega G, San-Blas F, San-Blas G. Geographic discrimination of Paracoccidioides brasiliensis strains by randomly amplified polymorphic DNA analysis. J Clin Microbiol 1998;36:1733–6.
Molinari-Madlum EEWI, Felipe MSS, Soares CMA. Virulence of Paracoccidioides brasiliensis isolates can be␣correlated to groups defined by random amplified polymorphic DNA analysis. Med Mycol 1999;37: 269–76.
Soares CM, Madlun EE, da Silva SP, Pereira M, Felipe MS. Characterization of Paracoccidioides brasiliensis isolates by random amplified polymorphic DNA analysis. J Clin Microbiol 1995;33:505–7.
Niño-Vega G, Calcagno AM, San-Blas G, San-Blas F, Gooday GW, Gow NAR. RFLP analysis reveals marked geographical isolation between strains of Paracoccidioides brasiliensis. Med Mycol 2000;38:437–41.
Hebeler-Barbosa F, Morais FV, Montenegro MR, Kuramae EE, Montes B, McEwen JG, et al. Comparison of the sequences of the internal transcribed spacer regions and PbGP43 genes of Paracoccidioides brasiliensis from patients and armadillos (Dasypus novemcinctus). J Clin Microbiol 2003;41:5735–7.
Morais FV, Barros TF, Fukada MK, Cisalpino PS, Puccia R. Polymorphism in the gene coding for the immunodominant antigen gp43 from the pathogenic fungus Paracoccidioides brasiliensis. J Clin Microbiol 2000;38:3960–6.
Carvalho KC, Ganiko L, Batista WL, Morais FV, Marques ER, Goldman GH, et al. Virulence of Paracoccidioides brasiliensis and gp43 expression in isolates bearing known PbGP43 genotype. Microb Infect 2005;7:55–65.
Matute DR, McEwen JG, Puccia R, Montes BA, San-Blas G, Bagagli E, Rauscher JT, Restrepo A, Morais F, Niño-Vega G, Taylor JW. Cryptic speciation and recombination in the fungus Paracoccidioides brasiliensis as revealed by gene genealogies. Mol Biol Evol 2006;23: 65–73.
Felipe MSS, Andrade RV, Arraes FBM, Nicola AM, Maranhão AQ, Torres FAG, et al Transcriptional profiles of the human pathogenic fungus Paracoccidioides brasiliensis in mycelium and yeast cells. J Biol Chem 2005;280:24706–14.
Visbal G., San-Blas G, Murgich J, Franco H. Paracoccidioides brasiliensis, paracoccidioidomycosis, and antifungal antibiotics. Curr Drug Targets: Infect Disord 2005;5:211–26.
Visbal G, Alvarez A, Moreno B, San-Blas G. Inhibitors of (S)-adenosyl-l-methionine: Δ24 _ sterol methyl transferase and Δ24 (28) -sterol methyl reductase as possible antifungal agents against Paracoccidioides brasiliensis. Antimicrob Agents Chemother 2003;47:2966–70.
Urbina JA, Vivas J, Visbal G, Contreras LM. Modification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi epimastigotes by Δ (24,25) sterol methyl transferase inhibitors and their combination with ketoconazole. Mol Biochem Parasitol 1995;73:199–210.
Urbina JA, Visbal G, Contreras LM, McLaughlin G, Docampo R. Inhibitors of Δ (24,25) sterol methyl transferase block sterol synthesis and cell proliferation in Pneumocystis carinii. Antimicrob Agents Chemother 1997;41: 1428–32.
San-Blas G, Urbina JA, Marchán E, Contreras LM, Sorais F, San-Blas F. Inhibition of Paracoccidioides brasiliensis by ajoene is associated with blockade of phosphatidylcholine biosynthesis. Microbiology 1997;143:1583–6.
Pfaller MA, Marco M, Messer SA, Jones RN. In vitro activity of two echinocandin derivatives, LY303366 and␣␣MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis 1998;30:251–255.
Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol 1998;36:2950–6.
Cantón E, Pemán J, Gobernado M, Alvarez E, Baquero F, Cisterna R, et al. Sensititre yeastone caspofungin susceptibility testing of Candida clinical isolates: correlation with results of NCCLS M27-A2 multicenter study. Antimicrob Agents Chemother 2005;49:1604–7.
Odds FC, Motyl M, Andrade R, Bille J, Canton E, Cuenca-Estrella M, et al. Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species. J Clin Microbiol 2004;42:3475–82.
Nakai T, Uno J, Ikeda F, Tawara S, Nishimura K, Miyaji M. In vitro antifungal activity of micafungin (FK463) against dimorphic fungi: comparison of yeast-like and mycelial forms. Antimicrob Agents Chemother 2003;47:1376– 1381.
Mendes-Giannini MJS, Bueno JP, Shikanai-Yashuda MA, Ferreira AW, Masuda A. Detection of 43,000-molecular-weight glycoprotein in sera of patients with paracoccidioidomycosis. J Clin Microbiol 1989;27:2842–5.
Del Negro GMB, Benard G, Assis CM, Vidal MS, Garcia NM, Otani C, et al. Lack of reactivity of paracoccidioidomycosis sera in the double immunodiffusion test with the gp43 antigen: report of two cases. J Med Vet Mycol 1995;33:113–6.
Puccia R, Travassos LR. 43-Kilodalton glycoprotein from Paracoccidioides brasiliensis: immunological reactions with sera from patients with paracoccidioidomycosis, histoplasmosis and Jorge Lobo disease. J Clin Microbiol 1991;29:1610–5.
Imai T, Sano A, Miyami Y, Watanabe K, Aoki FH, Branchini ML, et al. A new PCR primer for the identification of Paracoccidioides brasiliensis based on rRNA sequences coding the internal transcribed spacers (ITS) and 5.8s regions. Med Mycol 2000;38:323–6.
Gomes GM, Cisalpino PS, Taborda CP, Camargo ZP. PCR for diagnosis of paracoccidioidomycosis. J Clin Microbiol 2000;38:3478–80.
San-Blas G, Niño-Vega G, Barreto L, Hebeler-Barbosa F, Bagagli E, Olivero de Briceño R, et al. Primers for the clinical detection of Paracoccidioides brasiliensis. J Clin Microbiol 2005;49:4255–7.
Almeida SM, Queiroz-Telles F, Teive HAG, Ribeiro CEL, Werneck LC. Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings. J Infect 2004;48:193–8.
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San-Blas, G., Niño-Vega, G. Paracoccidioides brasiliensis: chemical and molecular tools for research on cell walls, antifungals, diagnosis, taxonomy. Mycopathologia 165, 183–195 (2008). https://doi.org/10.1007/s11046-007-9040-9
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DOI: https://doi.org/10.1007/s11046-007-9040-9