Diversidade genômica de isolados com origem clínica distinta de Leishmania infantum do Estado do Rio Grande do Norte

Abstract

Leishmaniasis is a complex of diseases with no preventable or therapeutic vaccine available. There is only a small set of drugs for treatment of these diseases, which evolve with distinct clinical outcomes from skin ulcers, to mucosal involvement or visceralization. The type of clinical presentation usually is associated with the infecting species of Leishmania. Leishmania infantum is the visceralizing species, causing visceral leishmaniasis, in Latin America, Europe and northern Africa and was introduced in the Americas by Europeans during colonization. Visceral leishmaniasis used to be a sporadic disease found in rural areas Northeast of Brazil, however with urbanization, outbreaks have been reported in periurban areas of major cities. L. infantum infection can evolve with control of the parasite without apparent clinical symptoms, with only a minority developing symptomatic disease. The reasons why one evolve with selfresolution and others develop full blown disease is not entirely understood, but seems to include host genetic susceptibility, comorbidity, sand fly exposure and potentially genetic variation in the infecting Leishmania species. Our ongoing study, have shown structural genome variations in several clinical Leishmania isolates obtained from people infected in the State of Rio Grande do Norte. Despite the different clinical patterns, the isolates´ genomes showed a high identity degree to each other, even the ones isolated from the 90 compared with the latest. However, the few found changes were sufficient for the isolation of the distinct groups by a principal component analysis, showing that the isolates from more recent years are more homogeneous among the population. Phylogenetic analyzes using Bayesian reconstruction methods have been made and supported the grouping patterns already seen in the foregoing results. Moreover by an Expanded Bayesian Skyline Plot it was possible to observe the growth of the genomic population of L. infantum compared with the 1990s. Changes were observed in the number of chromosome copies in all strains, but only chromosome 31 is presented as exclusively trisomic. This work presents evidence on patterns of L. infantum isolated genomes relating them to clinical characteristics of their hosts.