The impact of genetic recombination on pathogenic Leptospira.

Abstract

Leptospirosis is the most common zoonosis worldwide, and is increasingly common in poor urban communities, where there is inadequate sewage disposal and abundance of domestic and peridomestic animals. There are many risk factors associated with the disease, such as contaminated water exposure, close contact with animals, floods, recreational activities related to water, wet agriculture. The symptoms of leptospirosis are common to other infectious diseases and, if not treated, it can lead to meningitis, liver failure, kidney damage and death. Leptospirosis is caused by 38 pathogenic species of Leptospira, which are divided in almost 30 serogroups and more than 300 serovars. The serological classification (serogroups and serovars) is based on the expression of distinct lipopolysaccharide (LPS) antigens. These antigens are also associated to protective immunity; antibodies against a serovar protect from any member of the same serovar. Serologic and phylogenetic analyses are not congruent probably due to genetic recombination of LPS genes among different leptospiral species. To analyze the importance of recombination in leptospiral evolution, we performed a gene-by-gene tree topology comparison on closed genomes available in public databases at two levels: among core genomes of pathogenic species (34 recombinant among 1213 core genes), and among core genomes of L. interrogans isolates (178/798). We found that most recombinant genes code for proteins involved in translation, ribosomal structure and biogenesis, but also for cell wall, membrane and envelope biogenesis. Besides, our final results showed that half of LPS genes are recombinant (18/36). This is relevant because serovar classification and vaccine development are based on these epitopes. The frequent recombination of LPS-associated genes suggests that natural selection is promoting the survival of recombinant lineages. These results may help understanding the factors that make Leptospira a successful pathogen.