MLST reveals a clonal population structure for Cryptococcus neoformans molecular type VNI isolates from clinical sources in Amazonas, Northern-Brazil

• Published in: PloS one 2018-06, Vol.13 (6), p.e0197841-e0197841
• Main Authors: Rocha, Diego Fernando Silva, Cruz, Katia Santana, Santos, Carla Silvana da Silva, Menescal, Lizandra Stephanny Fernandes, Neto, João Ricardo da Silva, Pinheiro, Silviane Bezerra, Silva, Lucyane Mendes, Trilles, Luciana, Braga de Souza, João Vicente
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; Aged; AIDS; Amphotericin B; Antifungal agents; Biology and Life Sciences; Brazil - epidemiology; Clinical aspects; Clinical isolates; Computer and Information Sciences; Cryptococcosis; Cryptococcosis - epidemiology; Cryptococcus; Cryptococcus gattii; Cryptococcus neoformans; Cryptococcus neoformans - classification; Cryptococcus neoformans - physiology; Disease control; DNA sequencing; Environmental studies; Epidemiology; Female; Fluconazole; Fungal infections; Genetic analysis; Genetic aspects; Genetic relationship; HIV; Human immunodeficiency virus; Humans; Infections; Itraconazole; Laboratories; Lethality; Male; Medicine; Medicine and Health Sciences; Meningitis; Middle Aged; Molecular chains; Molecular structure; Multilocus Sequence Typing; Mycological Typing Techniques; Outbreaks; Pathogens; Patients; People and places; Phylogeny; Physiological aspects; Population; Population genetics; Population structure; Research and Analysis Methods; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197841

Cryptococcosis is considered endemic in Amazonas state, occurring more frequently in individuals with AIDS, who are predominantly infected by Cryptococcus neoformans molecular type VNI. Infections by Cryptococcus gattii VGII predominate in immunocompetent hosts from the American continent and are associated with outbreaks in North America, particularly the subtypes VGIIa and VGIIb, which are also present in the Brazilian Amazon region. Despite few environmental studies, several aspects of the molecular epidemiology of this disease in Amazonas remain unclear, including the limited use of multilocus sequence typing (MLST) to evaluate the genetic population structure of clinical isolates, mainly C. neoformans. Therefore, we used MLST to identify the sequence types of 38 clinical isolates of C. neoformans VNI and C. gattii VGII and used phylogenetic analysis to evaluate their genetic relationship to global isolates. Records of 30 patients were analyzed to describe the current scenario of cryptococcosis in the region and their associations with the different subtypes. Broth microdilution was also performed to determine the susceptibility profile to the antifungals amphotericin B, fluconazole and itraconazole. MLST identified that patients with HIV (n = 26) were exclusively affected by VNI strains with ST93, and among the VGII strains (n = 4), three STs (ST5, ST172 and the new ST445) were identified. An in-hospital lethality of 54% was observed in the HIV group, and there were no significant differences in the clinical aspects of the disease between the HIV and non-HIV groups of patients. In addition, all isolates were susceptible to the antifungals tested. Therefore, in Amazonas state, VNI isolates are a genetically monotypic group, with ST93 being highly important in HIV individuals.