Whole Genome Analysis of Leptospira licerasiae Provides Insight into Leptospiral Evolution and Pathogenicity

Abstract

The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010T and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics.

Role for cis -Acting RNA Sequences in the Temperature-Dependent Expression of the Multiadhesive Lig Proteins in Leptospira interrogans

“…Data from ongoing projects to obtain whole-genome sequences from a variety of Leptospira strains will aid in the analysis of candidate cis-and trans-acting factors that underlie the genetic regulatory circuitry controlling expression of leptospiral genes (65)(66)(67)(68)(69)(70). One outcome of these efforts is the computational identification of potential riboswitches, including those bound by cobalamin and thiamine pyrophosphate (68,71). Here we have presented experimental evidence for an RNA-based cis-acting element that controls gene expression in L. interrogans in response to temperature changes.…”

Multiple Posttranslational Modifications of Leptospira biflexa Proteins as Revealed by Proteomic Analysis

“…Leptospires can be broadly divided into host-associated species (including pathogens and the closely related intermediate species [1]) and free-living saprophytes, and Picardeau et al proposed that the host-associated species may have evolved from a free-living progenitor (2). Therefore, comparisons between species with different ecological niches may elucidate the mechanisms that allow host-associated species to infect, persist in, and sometimes cause fatal disease in their hosts.…”

Culture and molecular identification of microorganisms from Digital Dermatitis lesions in dairy cattle: Leptospira, an unexpected finding

“…L. fainei was successively cultured from two human patients with Weil's disease and antibody titers have been found in sera from cattle in Australia, France and Indonesia ( Chappel et al, 1996;Petersen et al, 2001). L. wolffii was identified as a potential pathogenic species, detected in infected humans, in sheep sera and dogs urine and can be potentially pathogenic to human and probably animal hosts (Zakeri et al, 2010); and L. licerasiae causes mild disease in humans and has been isolated from peridomestic and wild rodents and marsupials in Peruvian Amazon (Matthias et al, 2008;Ricaldi et al, 2012) and from environmental water (Saito et al, 2013). Krull et al (2015) showed that early BDD lesions had minimal populations of Treponema spp.…”

“…In contrast to Treponema species that fail to have significant genetic capabilities to break down the skin barrier (Krull et al, 2015), L. interrogans, the most common genotype in pathogenic Leptospira species, encodes a collagenase (colA gene), which was recently related to invasiveness and transmission of the spirochetes in cell monolayers and animals, being characterized as a novel and crucial virulence factor (Kassegne et al, 2014). Ricaldi et al (2012) …”