Caracterização genética e distribuição espacial dos isolados de Mycobacterium leprae em região de baixa prevalência no Brasil
Carregando...
Data
2016-02-26
Autores
Finardi, Amanda Juliane [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Desde 2005, São Paulo conseguiu eliminar a hanseníase como problema de saúde pública, no entanto, casos novos continuam a serem detectados em várias regiões do estado. Para entender sobre a estrutura populacional do Mycoabcterium leprae na região e utilizando clusterização como uma medida de transmissão recente, a genotipagem foi aplicada. Biópsias de pele de 128 casos de hanseníase de 15 Departamentos Regionais de Saúde foram submetidos à tipagem por MLVA e SNP. Nós obtivemos o genótipo completo para 95 isolados e 13 dos 16 VNTRs foram polimórficos. As repetições 12-5 e 18-8 tinham um número de cópias 6 ou 7 e 7 a 9, respectivamente, que são dificilmente observados em genótipos de outras regiões do país. Uma árvore construída por UPGMA demonstrou a existência de dois grandes grupos e essa separação parece ter ocorrido principalmente pelo STR 18-8, que apresentou 6-9 cópias somente no segundo grupo. Foi construída uma MST com 414 genótipos completos desse presente estudo juntamente com genótipos de outros estados do país que também demostraram dois grandes grupos. Parte das cepas de SP foram agrupadas com cepas do estado de MT e outras foram agrupadas próximas as cepas do RJ. Cepas de PE e CE, também foram agrupadas entre si. A análise de sequenciamento de SNP da região folP1 e rpoB apresentaram resistência à droga em 5 casos para folP1, sendo que em um desses casos, também para rpoB. Nossos dados sugerem que os dois grupos de M. leprae existentes no estado de SP surgiram a partir de dois ancestrais diferentes e que a tipagem por VNTR em hanseníase, pela exclusão de determinados marcadores, principalmente determinada por análise de SNP, pode auxiliar na filogenia. Nós observamos a predominância de 97% de SNP tipo 3, mas subtipagem adicional deverá ser realizada para verificar a associação com tipos de VNTR.
Since 2005, São Paulo claims to have eliminated leprosy as a public health problem but new cases continue being detected in several regions of the state. To learn about the population structure of Mycobacterium leprae in the region and use clustering as a measure for recent transmission, genotyping was performed. Skin biopsy samples from 128 leprosy cases from 15 regional departments of health were submitted to MLVA and SNP typing. We obtained complete genotypes for 95 isolates and 13 of the 16 VNTRs were polymorphic. The repeats 12-5 and 18-8 had a copy number of 6 or 7 and 7 to 9 respectively that are hardly observed in genotypes from other regions of the country. A UPGMA based tree demonstrated the existence of two major groups and this separation seems to be driven mainly by STR 18-8, presenting 6-9 copies only in the second group. A MST constructed with 414 complete genotypes of the present study together with genotypes from other states of the country also demonstrated two major groups. On part of the SP strains were grouped with the strains from MT and another close to RJ strains; strains from PE and CE, two states from Northeast Brazil were also grouped. Sequence analysis of folP1 and rpoB presented drug resistence associated SNPs in folP1 in five cases and rpoB in one of these. Our data suggest that the two major groups of M. leprae exist in Sao Paulo emerged from two different ancestors and that VNTR typing in leprosy, upon the exclusion of the proper markers, can add on phylogeny mostly determined by SNP analysis. We observed the predominance of 97% of the SNP type 3 but further subtyping should be performed in order to associate with VNTR types.
Since 2005, São Paulo claims to have eliminated leprosy as a public health problem but new cases continue being detected in several regions of the state. To learn about the population structure of Mycobacterium leprae in the region and use clustering as a measure for recent transmission, genotyping was performed. Skin biopsy samples from 128 leprosy cases from 15 regional departments of health were submitted to MLVA and SNP typing. We obtained complete genotypes for 95 isolates and 13 of the 16 VNTRs were polymorphic. The repeats 12-5 and 18-8 had a copy number of 6 or 7 and 7 to 9 respectively that are hardly observed in genotypes from other regions of the country. A UPGMA based tree demonstrated the existence of two major groups and this separation seems to be driven mainly by STR 18-8, presenting 6-9 copies only in the second group. A MST constructed with 414 complete genotypes of the present study together with genotypes from other states of the country also demonstrated two major groups. On part of the SP strains were grouped with the strains from MT and another close to RJ strains; strains from PE and CE, two states from Northeast Brazil were also grouped. Sequence analysis of folP1 and rpoB presented drug resistence associated SNPs in folP1 in five cases and rpoB in one of these. Our data suggest that the two major groups of M. leprae exist in Sao Paulo emerged from two different ancestors and that VNTR typing in leprosy, upon the exclusion of the proper markers, can add on phylogeny mostly determined by SNP analysis. We observed the predominance of 97% of the SNP type 3 but further subtyping should be performed in order to associate with VNTR types.
Descrição
Palavras-chave
Mycobacterium leprae, SNP, VNTR, Hanseníase, Transmissão