MLST-based population genetic analysis in a global context reveals clonality amongst Cryptococcus neoformans var. grubii VNI isolates from HIV patients in southeastern Brazil

Kennio Ferreira-Paim, Leonardo Andrade-Silva, Fernanda M. Fonseca, Thatiana B. Ferreira, Delio J. Mora, Juliana Andrade-Silva, Aziza Khan, Aiken Dao, Eduardo C. Reis, Margarete T G Almeida, Andre Maltos, Virmondes R. Junior, Luciana Trilles, Volker Rickerts, Ariya Chindamporn, Jane E Sykes, Massimo Cogliati, Kirsten Nielsen, Teun Boekhout, Matthew FisherJune Kwon-Chung, David M. Engelthaler, Marcia Lazéra, Wieland Meyer, Mario L. Silva-Vergara

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Abstract

Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients. All the isolates were found to be C. neoformans var. grubii major molecular type VNI and mating type locus alpha. Twelve were identified as diploid by flow cytometry, being homozygous (AαAα) for the mating type and by PCR screening of the STE20, GPA1, and PAK1 genes. Using the ISHAM consensus multilocus sequence typing (MLST) scheme, 13 sequence types (ST) were identified, with one being newly described. ST93 was identified from 81 (75%) of the clinical isolates, while ST77 and ST93 were identified from 19 (54%) and 10 (29%) environmental isolates, respectively. The southeastern Brazilian isolates had an overwhelming clonal population structure. When compared with populations from different continents based on data extracted from the ISHAM-MLST database (mlst.mycologylab.org) they showed less genetic variability. Two main clusters within C. neoformans var. grubii VNI were identified that diverged from VNB around 0.58 to 4.8 million years ago.

Original languageEnglish (US)
Article numbere0005223
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2017

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Multilocus Sequence Typing
Cryptococcus neoformans
Population Genetics
Brazil
HIV
Cryptococcosis
Fatal Outcome
Mycoses
Genetic Structures
Consensus Sequence
Diploidy
Meningitis
Population
Flow Cytometry
Public Health
Databases
Polymerase Chain Reaction
Mortality
Genes
Therapeutics

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

MLST-based population genetic analysis in a global context reveals clonality amongst Cryptococcus neoformans var. grubii VNI isolates from HIV patients in southeastern Brazil. / Ferreira-Paim, Kennio; Andrade-Silva, Leonardo; Fonseca, Fernanda M.; Ferreira, Thatiana B.; Mora, Delio J.; Andrade-Silva, Juliana; Khan, Aziza; Dao, Aiken; Reis, Eduardo C.; Almeida, Margarete T G; Maltos, Andre; Junior, Virmondes R.; Trilles, Luciana; Rickerts, Volker; Chindamporn, Ariya; Sykes, Jane E; Cogliati, Massimo; Nielsen, Kirsten; Boekhout, Teun; Fisher, Matthew; Kwon-Chung, June; Engelthaler, David M.; Lazéra, Marcia; Meyer, Wieland; Silva-Vergara, Mario L.

In: PLoS Neglected Tropical Diseases, Vol. 11, No. 1, e0005223, 01.01.2017.

Research output: Contribution to journalArticle

Ferreira-Paim, K, Andrade-Silva, L, Fonseca, FM, Ferreira, TB, Mora, DJ, Andrade-Silva, J, Khan, A, Dao, A, Reis, EC, Almeida, MTG, Maltos, A, Junior, VR, Trilles, L, Rickerts, V, Chindamporn, A, Sykes, JE, Cogliati, M, Nielsen, K, Boekhout, T, Fisher, M, Kwon-Chung, J, Engelthaler, DM, Lazéra, M, Meyer, W & Silva-Vergara, ML 2017, 'MLST-based population genetic analysis in a global context reveals clonality amongst Cryptococcus neoformans var. grubii VNI isolates from HIV patients in southeastern Brazil', PLoS Neglected Tropical Diseases, vol. 11, no. 1, e0005223. https://doi.org/10.1371/journal.pntd.0005223
Ferreira-Paim, Kennio ; Andrade-Silva, Leonardo ; Fonseca, Fernanda M. ; Ferreira, Thatiana B. ; Mora, Delio J. ; Andrade-Silva, Juliana ; Khan, Aziza ; Dao, Aiken ; Reis, Eduardo C. ; Almeida, Margarete T G ; Maltos, Andre ; Junior, Virmondes R. ; Trilles, Luciana ; Rickerts, Volker ; Chindamporn, Ariya ; Sykes, Jane E ; Cogliati, Massimo ; Nielsen, Kirsten ; Boekhout, Teun ; Fisher, Matthew ; Kwon-Chung, June ; Engelthaler, David M. ; Lazéra, Marcia ; Meyer, Wieland ; Silva-Vergara, Mario L. / MLST-based population genetic analysis in a global context reveals clonality amongst Cryptococcus neoformans var. grubii VNI isolates from HIV patients in southeastern Brazil. In: PLoS Neglected Tropical Diseases. 2017 ; Vol. 11, No. 1.
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AU - Fonseca, Fernanda M.

AU - Ferreira, Thatiana B.

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AU - Nielsen, Kirsten

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AU - Fisher, Matthew

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