Genome Sequence of the Saprophyte Leptospira biflexa Provides Insights into the Evolution of Leptospira and the Pathogenesis of Leptospirosis

Abstract

Leptospira biflexa is a free-living saprophytic spirochete present in aquatic environments. We determined the genome sequence of L. biflexa, making it the first saprophytic Leptospira to be sequenced. The L. biflexa genome has 3,590 protein-coding genes distributed across three circular replicons: the major 3,604 chromosome, a smaller 278-kb replicon that also carries essential genes, and a third 74-kb replicon. Comparative sequence analysis provides evidence that L. biflexa is an excellent model for the study of Leptospira evolution; we conclude that 2052 genes (61%) represent a progenitor genome that existed before divergence of pathogenic and saprophytic Leptospira species. Comparisons of the L. biflexa genome with two pathogenic Leptospira species reveal several major findings. Nearly one-third of the L. biflexa genes are absent in pathogenic Leptospira. We suggest that once incorporated into the L. biflexa genome, laterally transferred DNA undergoes minimal rearrangement due to physical restrictions imposed by high gene density and limited presence of transposable elements. In contrast, the genomes of pathogenic Leptospira species undergo frequent rearrangements, often involving recombination between insertion sequences. Identification of genes common to the two pathogenic species, L. borgpetersenii and L. interrogans, but absent in L. biflexa, is consistent with a role for these genes in pathogenesis. Differences in environmental sensing capacities of L. biflexa, L. borgpetersenii, and L. interrogans suggest a model which postulates that loss of signal transduction functions in L. borgpetersenii has impaired its survival outside a mammalian host, whereas L. interrogans has retained environmental sensory functions that facilitate disease transmission through water.

High-coverage proteome analysis reveals the first insight of protein modification systems in the pathogenic spirochete Leptospira interrogans

“…Similarly, the start codons of another six proteincoding genes were found to be wrongly annotated and were eventually rectified according to the proteomic data. Among protein-coding genes in the serovar Lai genome, 73 genes were previously predicted to be pseudogenes by Adler and coworkers [6]. To our surprise, we detected peptides uniquely assigned to five proteins, which are encoded by pseudogenes (LA0703, LA1005, LA2083, LA4202 and LB007).…”

“…Despite advances in prevention and therapy, the molecular mechanisms of pathogenesis in leptospirosis remain almost completely unknown. The genome sequences of the pathogenic L. interrogans serovar Lai and serovar Copenhageni, the pathogenic L. borgpetersenii serovar Hardjo and the saprophytic L. biflexa serovar Patoc have been reported [3][4][5][6]. The accomplishment of these sequencing projects greatly facilitated the studies of Leptospira physiology and pathology at the genomic [4][5][6], transcriptomic [7,8] and proteomic levels [9][10][11][12][13][14].…”

Insights into Leptospirosis, a Neglected Disease

“…Both these genomes are larger and differ considerably from those of the related spirochetes, Treponema pallidum and Borrelia burgdorferi, indicating their divergence from the phylum. Today, two additional genome sequences, namely that of L. borgpetersenii serovar Hardjo strains L550, JB197 and L. biflexa serovar Patoc strain Patoc 1 (Ames strain) [Picardeau et al, 2008] are available…”

“…Fur, encoded by LB183, one of the fur genes present in the vicinity of hbpA (LB191) possibly acts by binding to the Fur box (5' GATAATCATAATAATTT) located upstream of hbpA [Sritharan et al, 2005]. Nascimento et al, 2004;Picardeau et al, 2008;Ren et al, 2003]. …”

Leptospirose E Seu Aspecto Ocupacional - Revisão De Literatura

“…as bactérias podem ser divididas em bactérias saprófitas e bacté-rias patogênicas, cuja patogenicidade ainda é indeterminada (PICARDEAU et al, 2008). Possivelmente as leptospiras de vida livre são as bactérias ancestrais, a qual a capacidade de sobreviver em hospedeiros tenha sido adquirida posteriormente neste gênero (FAINE et al, 1999).…”