Genotypes and population genetics of cryptococcus neoformans and cryptococcus gattii species complexes in Europe and the mediterranean area

Massimo Cogliati (1) , Marie Desnos-Ollivier (2) , Ilka Mccormick-Smith (3) , Volker Rickerts (3) , Kennio Ferreira-Paim (4) , Wieland Meyer (5) , Teun Boekhout (6) , Ferry Hagen (7) , Bart Theelen (7) , Joäo Inácio (8) , Beatriz Alonso (8) , Maria Colom (9) , Luciana Trilles (10) , Maria Montagna (11) , Antonella de Donno (12) , Serdar Susever (13) , Cagri Ergin (14) , Aristea Velegraki (15) , Mohamed Ellabib (16) , Simona Nardoni (17) , Cristina Macci (18) , Laura Trovato (19) , Ludovico Dipineto (20) , Sevim Akcaglar (21) , Emilija Mlinaric-Missoni (22) , Sébastien Bertout (23, 24) , Ana C.F. Vencá (25) , Ana Sampaio (26) , Giuseppe Criseo (27) , Stephane Ranque (28) , Nilgün Çerikçioğlu (29) , Anna Marchese (30) , Luigi Vezzulli (30) , Macit Ilkit (31) , Vincenzo Pasquale (32) , Itzhack Polacheck (33) , Shawn Lockhart (34)

1 UNIMI - Università degli Studi di Milano = University of Milan
2 IP - Institut Pasteur [Paris]
3 RKI - Robert Koch Institute [Berlin]
4 The University of Sydney
5 The Westmead Institute for Medical Research
6 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
7 WI - Westerdijk Fungal Biodiversity Institute [Utrecht]
8 University of Brighton
9 UMH - Universidad Miguel Hernández [Elche]
10 FIOCRUZ - Fundação Oswaldo Cruz / Oswaldo Cruz Foundation
11 UNIBA - Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro
12 Università del Salento [Lecce]
13 Cyprus Near East University
14 Pamukkale University
15 NKUA - National and Kapodistrian University of Athens
16 University of Tripoli - University Al Fateh
17 University of Pisa - Università di Pisa
18 IRET - Research Institute on Terrestrial Ecosystems [CNR, Italy]
19 Unict - Università degli studi di Catania = University of Catania
20 University of Naples Federico II = Università degli studi di Napoli Federico II
21 Uludağ Üniversitesi = Uludag University
22 CIPH - Croatian Institute of Public Health [Zagreb]
23 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
24 UM - Université de Montpellier
25 IHMT - Instituto de Higiene e Medicina Tropical
26 UTAD - Universidade de Trás-os-Montes e Alto Douro
27 University of Messina
28 VITROME - Vecteurs - Infections tropicales et méditerranéennes
29 Marmara University [Kadıköy - İstanbul]
30 UniGe - Università degli studi di Genova = University of Genoa
31 Cukurova University
32 PARTHENOPE - Università degli Studi di Napoli “Parthenope” = University of Naples
33 Hadassah Hebrew University Medical Center [Jerusalem]
34 CDC - Centers for Disease Control and Prevention [Atlanta]

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.

Mots clés: Cryptococcus neoformans; Cryptococcus gattii; MLST; Population genetics; Europe

Domaines: Bactériologie; Virologie; Parasitologie; Cardiologie et système cardiovasculaire; Maladies émergentes; Maladies infectieuses

Massimo Cogliati, Marie Desnos-Ollivier, Ilka Mccormick-Smith, Volker Rickerts, Kennio Ferreira-Paim, et al.. Genotypes and population genetics of cryptococcus neoformans and cryptococcus gattii species complexes in Europe and the mediterranean area. Fungal Genetics and Biology, 2019, 129, pp.16-29. ⟨10.1016/j.fgb.2019.04.001⟩. ⟨hal-02263653⟩