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Heterozygosis and Pathogenicity of Cryptococcus neoformans AD-Hybrid Isolates

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Abstract

Nineteen Cryptococcus neoformans AD-hybrid isolates were investigated to assess whether hybrid genomic background could affect virulence in a mouse model. The level of heterozygosity of each strain was analyzed using primers specific for allele A and D of 15 polymorphic genes. Virulence was tested in a mouse model of systemic infection by measuring time of survival. In addition, the putative virulence attributes, melanin, phospholipase, and capsule production, as well as growth at 39°C and UV sensitivity were investigated. Eight strains showed to be heterozygous in up to 70% of loci, other eight strains were heterozygous in less than 60% of loci, while the remaining three strains were homozygous at all tested loci. Mice infected with hybrids with a high percentage of heterozygosis showed significantly (P < 0.01) shorter survival than mice infected with the other hybrids. Mortality was not correlated with the mating-type locus pattern, as well as it was not correlated with the level of expression of the different virulence attributes investigated. The present study confirms that hybridization in C. neoformans could represent an important evolutionary driving force in increasing the fitness of this yeast in the environment and in the host.

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References

  1. Heitman J, Kozel R, Kwon-Chung KJ, Perfect JR, Casadevall A. Cryptococcus. From human pathogen to model yeast. Washington, DC: ASM Press; 2011.

    Google Scholar 

  2. Capoor MR, Mandal P, Deb M, Aggarwal P, Banerjee U. Current scenario of cryptococcosis and antifungal susceptibility pattern in India: a cause for reappraisal. Mycoses. 2008;51(3):258–65.

    Article  PubMed  CAS  Google Scholar 

  3. Hakim JG, Gangaidzo IT, Heyderman RS, Mielke J, Mushangi E, Taziwa A, et al. Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients. AIDS. 2000;14:1401–7.

    Article  PubMed  CAS  Google Scholar 

  4. Helbok R, Pongpakdee S, Yenjun S, Dent W, Beer R, Lackner P, et al. Chronic meningitis in Thailand—Clinical characteristics, laboratory data and outcome in patients with specific reference to tuberculosis and cryptococcosis. Neuroepidemiol. 2006;26:37–44.

    Article  CAS  Google Scholar 

  5. Ikeda R, Shinoda T, Fukazawa Y, Kaufman L. Antigenic characterization of Cryptococcus neoformans serotypes and its application to serotyping of clinical isolates. J Clin Microbiol. 1982;16:22–9.

    PubMed  CAS  Google Scholar 

  6. Viviani MA, Wen H, Roverselli A, Caldarelli-Stefano R, Cogliati M, Ferrante P, et al. Identification by polymerase chain reaction fingerprinting of Cryptococcus neoformans serotype AD. J Med Vet Mycol. 1997;35:355–60.

    Article  PubMed  CAS  Google Scholar 

  7. Boekhout T, Theelen B, Diaz M, Fell JW, Hop WCJ, Abeln ECA, et al. Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans. Microbiology. 2001;147:891–907.

    PubMed  CAS  Google Scholar 

  8. Meyer W, Castaneda A, Jackson S, Huynh M, Castaneda E. IberoAmerican Cryptococcal study group. Molecular typing of IberoAmerican Cryptococcus neoformans isolates. Emerg Infect Dis. 2003;9:189–95.

    PubMed  Google Scholar 

  9. Franzot SP, Salkin IF, Casadevall A. Cryptococcus neoformans var. grubii: separate varietal status for Cryptococcus neoformans serotype A isolates. J Clin Microbiol. 1999;37:838–40.

    PubMed  CAS  Google Scholar 

  10. Meyer W, Aanensen DM, Boekhout T, Cogliati M, Diaz MR, Esposto MC, et al. Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii. Med Mycol. 2009;47:561–70.

    Article  PubMed  CAS  Google Scholar 

  11. Cogliati M, Esposto MC, Clarke DL, Wickes BL, Viviani MA. Origin of Cryptococcus neoformans var. neoformans diploid strains. J Clin Microbiol. 2001;39:3889–94.

    Article  PubMed  CAS  Google Scholar 

  12. Lengeler KB, Cox GM, Heitman J. Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus. Infect Immun. 2001;69:115–22.

    Article  PubMed  CAS  Google Scholar 

  13. Viviani MA, Antinori S, Cogliati M, Esposto MC, Pinsi G, Casari S, et al. European Confederation of Medical Mycology (ECMM) prospective survey of cryptococcosis: report from Italy. Med Mycol. 2002;40:507–17.

    Google Scholar 

  14. Viviani MA, Cogliati M, Esposto MC, Lemmer K, Tintelnot K, Valiente MFC, et al. Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe. FEMS Yeast Res. 2006;6:614–9.

    Article  PubMed  CAS  Google Scholar 

  15. Kohno S, Varma A, Kwon-Chung KJ, Hara K. Epidemiology studies of clinical isolates of Cryptococcus neoformans of Japan by restriction fragment length polymorphism. Kansenshogaku Zasshi. 1994;68:1512–7.

    PubMed  CAS  Google Scholar 

  16. Yan Z, Li XG, Xu JP. Geographic distribution of mating type alleles of Cryptococcus neoformans in four areas of the United States. J Clin Microbiol. 2002;40:965–72.

    Article  PubMed  Google Scholar 

  17. Lin XR, Litvintseva AP, Nielsen K, Patel S, Floyd A, Mitchell TG, et al. αADα hybrids of Cryptococcus neoformans: evidence of same-sex mating in nature and hybrid fitness. PLoS Genet. 2007;3:e186.

    Article  Google Scholar 

  18. Chaturvedi V, Fan JJ, Stein B, Behr MJ, Samsonoff WA, Wickes BL, et al. Molecular genetic analyses of mating pheromones reveal intervariety mating or hybridization in Cryptococcus neoformans. Infect Immun. 2002;70:5225–35.

    Article  PubMed  CAS  Google Scholar 

  19. Barchiesi F, Cogliati M, Esposto MC, Spreghini E, Schimizzi M, Wickes BL, et al. Comparative analysis of pathogenicity of Cryptococcus neoformans serotypes A, D and AD in murine cryptococcosis. J Infect. 2005;51:10–6.

    Article  PubMed  CAS  Google Scholar 

  20. Lin XR, Nielsen K, Patel S, Heitman J. Impact of mating type, serotype, and ploidy on the virulence of Cryptococcus neoformans. Infect Immun. 2008;76:2923–38.

    Article  PubMed  CAS  Google Scholar 

  21. Shahid M, Han S, Yoell H, Xu JP. Fitness distribution and transgressive segregation across 40 environments in a hybrid progeny population of the human-pathogenic yeast Cryptococcus neoformans. Genome. 2008;51:272–81.

    Article  PubMed  Google Scholar 

  22. Mallet J. Hybridization as an invasion of the genome. Trends Ecol Evol. 2005;20:229–37.

    Article  PubMed  Google Scholar 

  23. Cogliati M, Esposto MC, Tortorano AM, Viviani MA. Cryptococcus neoformans population includes hybrid strains homozygous at mating-type locus. FEMS Yeast Res. 2006;6:608–13.

    Article  PubMed  CAS  Google Scholar 

  24. Kwon-Chung KJ, Polacheck I, Popkin TJ. Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice. J Bacteriol. 1982;150:1414–21.

    PubMed  CAS  Google Scholar 

  25. Price MF, Wilkinson ID, Gentry LO. Plate method for detection of phospholipase activity in Candida albicans. 1982:7–14.

  26. Zaragoza O, Casadevall A. Experimental modulation of capsule size in Cryptococcus neoformans. Biol Proced Online. 2004;6:10–5.

    Article  PubMed  CAS  Google Scholar 

  27. Sun S, Xu JP. Genetic analyses of a hybrid cross between serotypes A and D strains of the human pathogenic fungus Cryptococcus neoformans. Genetics. 2007;177:1475–86.

    Article  PubMed  CAS  Google Scholar 

  28. Sun S, Xu J. Chromosomal rearrangements between serotype A and D in Cryptococcus neoformans. PlosOne. 2009;4:1–17.

    Google Scholar 

  29. Li W, Ni M, Averette AF, Desnos-Ollivier M, Dromer F, Heitman J. Genetic diversity and genomic plasticity of Cryptococccus neoformans AD hybrids. In: 8th international conference on Cryptococcus and Cryptococcosis, 1–5 May 2011, Charleston, SC, USA. Poster 15.

  30. Wang P, Nichols CB, Lengeler MB, Cardenas ME, Cox GM, Perfect JR, et al. Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans. Eukaryot Cell. 2002;1:257–72.

    Article  PubMed  CAS  Google Scholar 

  31. Nielsen K, Marra RE, Hagen F, Boekhout T, Mitchell TG, Cox GM, et al. Interaction between genetic background and the mating-type locus in Cryptococcus neoformans virulence potential. Genetics. 2005;171:975–83.

    Article  PubMed  CAS  Google Scholar 

  32. Hicks JK, D’Souza CA, Cox GM, Heitman J. Cyclic AMP-dependent protein kinase catalytic subunits have divergent roles in virulence factor production in two varieties of the fungal pathogen Cryptococcus neoformans. Eukaryot Cell. 2004;3:14–26.

    Article  PubMed  CAS  Google Scholar 

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Cogliati, M., Barchiesi, F., Spreghini, E. et al. Heterozygosis and Pathogenicity of Cryptococcus neoformans AD-Hybrid Isolates. Mycopathologia 173, 347–357 (2012). https://doi.org/10.1007/s11046-011-9467-x

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  • DOI: https://doi.org/10.1007/s11046-011-9467-x

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