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A total of 476 European isolates (310 Cryptococcus neoformans var. grubii, 150 C. neoformans var. neoformans, and 16 C. gattii species complex) from both clinical and environmental sources were analyzed by multi-locus sequence typing. Phylogenetic and population genetic analyses were performed. Sequence analysis identified 74 sequence types among C. neoformans var. neoformans (VNIV), 65 among C. neoformans var. grubii (56 VNI, 8 VNII, 1 VNB), and 5 among the C. gattii species complex (4 VGI and 1 VGIV) isolates. ST23 was the most frequent genotype (22%) among VNI isolates which were mostly grouped in a large clonal cluster including 50% of isolates. Among VNIV isolates, a predominant genotype was not identified. A high percentage of autochthonous STs were identified in both VNI (71%) and VNIV (96%) group of isolates. The 16 European C. gattii species complex isolates analyzed in the present study originated all from the environment and all belonged to a large cluster endemic in the Mediterranean area. Population genetic analysis confirmed that VNI group of isolates were characterized by low variability and clonal expansion while VNIV by a higher variability and a number of recombination events. However, when VNI and VNIV environmental isolates were compared, they showed a similar population structure with a high percentage of shared mutations and the absence of fixed mutations. Also linkage disequilibrium analysis reveals differences between clinical and environmental isolates showing a key role of PLB1 allele combinations in host infection as well as the key role of LAC1 allele combinations for survival of the fungus in the environment. The present study shows that genetic comparison of clinical and environmental isolates represents a first step to understand the genetic characteristics that cause the shift of some genotypes from a saprophytic to a parasitic life style. C1 [Cogliati, Massimo] Univ Milan, Dip Sci Biomed Sallee, Via Pascal 36, I-20133 Milan, Italy. [Desnos-Ollivier, Marie] CNRS, UMR2000, Natl Reference Ctr Invas Mycoses & Antifungal, Inst Pasteur,Mol Mycol Unit, Paris, France. [McCormick-Smith, Ilka; Rickerts, Volker] Robert Koch Inst, Berlin, Germany. [Ferreira-Paim, Kennio; Meyer, Wieland] Univ Sydney, Marie Bashier Inst Emerging Infect Dis & Biosecur, Westmead Inst Med Res,Sydney Med Sch,Westmead Cli, Mol Mycol Res Lab,Ctr Infect Dis,Fac Med & Hlth,W, Westmead, NSW, Australia. [Ferreira-Paim, Kennio] Univ Fed Triangulo Mineiro, Dept Microbiol, Uberaba, MG, Brazil. [Boekhout, Teun; Hagen, Ferry; Theelen, Bart] Westerdijk Fungal Biodivers Inst, Utrecht, Netherlands. [Boekhout, Teun] Univ Amsterdam, IBED, Amsterdam, Netherlands. [Inacio, Joao; Alonso, Beatriz] Univ Brighton, Sch Pharm & Biomol Sci, Brighton, E Sussex, England. [Alonso, Beatriz] Hosp Gegorio Maranon, Inst Invest Sanitaria Gregorio Maranon IisGM, Madrid, Spain. [Colom, Maria F.] Univ Miguel Hernandez, Alicante, Spain. [Trilles, Luciana] Fundacao Oswaldo Cruz, FIOCRUZ, Rio De Janeiro, Brazil. [Montagna, Maria Teresa] Univ Bari Aldo Moro, Bari, Italy. [De Donno, Antonella] Univ Salento, DiSTeBA, Lecce, Italy. [Susever, Serdar] Cyprus Near East Univ, Nicosia, Cyprus. [Ergin, Cagri] Pamukkale Univ, Denizli, Turkey. [Velegraki, Aristea] Univ Athens, Med Sch, Athens, Greece. [Ellabib, Mohamed S.] Univ Tripoli, Med Coll, Tripoli, Libya. [Nardoni, Simona] Univ Pisa, Pisa, Italy. [Macci, Cristina] CNR, Res Inst Terr Ecosystems IRET, Pisa, Italy. [Trovato, Laura] Univ Catania, Catania, Italy. [Dipineto, Ludovico] Univ Napoli Federico II, Naples, Italy. [Akcaglar, Sevim] Uludag Univ, Sch Med, Bursa, Turkey. [Mlinaric-Missoni, Emilija] Croatian Natl Inst Publ Hlth, Zagreb, Croatia. [Bertout, Sebastien] Univ Montpellier, Unite Mixte Int Rech Translat Infect VIH & Malad, Montpellier, France. [Venca, Ana C. F.] Inst Higiene & Med Trop, Lisbon, Portugal. [Sampaio, Ana C.] Univ Tras os Montes & Alto Douro, CITAB, Quinta Prados, Vila Real, Portugal. [Criseoa, Giuseppe] Univ Messina, Dept Chem Biol Pharmaceut & Environm Sci, Messina, Italy. [Ranque, Stephane] Aix Marseille Univ, IHU Mediterranee Infect, AP HM, IRD,SSA,VITROME, Marseille, France. [Cerikcioglu, Nilgun] Marmara Univ, Sch Med, Istanbul, Turkey. [Marchese, Anna] Univ Genoa, IRCCS Policlin San Martino Genova, Sez Microbiol DISC, Genoa, Italy. [Vezzulli, Luigi] Univ Genoa, Dipartimento Sci Terra Ambiente & Vita DISTAV, Genoa, Italy. [Ilkit, Macit] Univ Cukurova Saricam, Adana, Turkey. [Pasquale, Vincenzo] Univ Napoli Parthenope, Naples, Italy. [Polacheck, Itzhack] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. [Lockhart, Shawn R.] Ctr Dis Control & Prevent, Atlanta, GA USA. |