Leptospira species molecular epidemiology in the genomic era

Caimi, Karina; Repetto, Silvia; Varni, Vanina Delia; Ruybal, Paula

doi:10.1016/j.meegid.2017.08.013

Cited by 11 publications

(10 citation statements)

References 48 publications

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“…Interestingly enough, the subclades P1 and P2 seem to be constituted by multiple small subgroups, representing a high level of diversity. As a note the segmentation of the subclade P1 in groups have been already described [9, 11, 15, 43]. Also, the species forming the new subclade S2 are clearly among the most diverse in ANI values, consistent with the long branches in the phylogenetic tree.…”

Section: Discussionsupporting

confidence: 75%

Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics

et al. 2019

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The causative agents of leptospirosis are responsible for an emerging zoonotic disease worldwide. One of the major routes of transmission for leptospirosis is the natural environment contaminated with the urine of a wide range of reservoir animals. Soils and surface waters also host a high diversity of non-pathogenic Leptospira and species for which the virulence status is not clearly established. The genus Leptospira is currently divided into 35 species classified into three phylogenetic clusters, which supposedly correlate with the virulence of the bacteria. In this study, a total of 90 Leptospira strains isolated from different environments worldwide including Japan, Malaysia, New Caledonia, Algeria, mainland France, and the island of Mayotte in the Indian Ocean were sequenced. A comparison of average nucleotide identity (ANI) values of genomes of the 90 isolates and representative genomes of known species revealed 30 new Leptospira species. These data also supported the existence of two clades and 4 subclades. To avoid classification that strongly implies assumption on the virulence status of the lineages, we called them P1, P2, S1, S2. One of these subclades has not yet been described and is composed of Leptospira idonii and 4 novel species that are phylogenetically related to the saprophytes. We then investigated genome diversity and evolutionary relationships among members of the genus Leptospira by studying the pangenome and core gene sets. Our data enable the identification of genome features, genes and domains that are important for each subclade, thereby laying the foundation for refining the classification of this complex bacterial genus. We also shed light on atypical genomic features of a group of species that includes the species often associated with human infection, suggesting a specific and ongoing evolution of this group of species that will require more attention. In conclusion, we have uncovered a massive species diversity and revealed a novel subclade in environmental samples collected worldwide and we have redefined the classification of species in the genus. The implication of several new potentially infectious Leptospira species for human and animal health remains to be determined but our data also provide new insights into the emergence of virulence in the pathogenic species.

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Section: Discussionsupporting

confidence: 75%

Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics

et al. 2019

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“…The classical MLST schemes were developped using six or seven genes with a focus on pathogenic Leptospira species [29, 45, 73]. More recently, a new MLST scheme was proposed and applied to a wider collection of strains, including a few intermediate species [46, 62]. However, none of these MLST methods enables the inclusion of all major Leptospira lineages, including saprophytic strains.…”

Section: Discussionmentioning

confidence: 99%

Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance

et al. 2019

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Leptospira is a highly heterogeneous bacterial genus that can be divided into three evolutionary lineages and >300 serovars. The causative agents of leptospirosis are responsible of an emerging zoonotic disease worldwide. To advance our understanding of the biodiversity of Leptospira strains at the global level, we evaluated the performance of whole-genome sequencing (WGS) as a genus-wide strain classification and genotyping tool. Herein we propose a set of 545 highly conserved loci as a core genome MLST (cgMLST) genotyping scheme applicable to the entire Leptospira genus, including non-pathogenic species. Evaluation of cgMLST genotyping was undertaken with 509 genomes, including 327 newly sequenced genomes, from diverse species, sources and geographical locations. Phylogenetic analysis showed that cgMLST defines species, clades, subclades, clonal groups and cgMLST sequence types (cgST), with high precision and robustness to missing data. Novel Leptospira species, including a novel subclade named S2 (saprophytes 2), were identified. We defined clonal groups (CG) optimally using a single-linkage clustering threshold of 40 allelic mismatches. While some CGs such as L . interrogans CG6 (serogroup Icterohaemorrhagiae) are globally distributed, others are geographically restricted. cgMLST was congruent with classical MLST schemes, but had greatly improved resolution and broader applicability. Single nucleotide polymorphisms within single cgST groups was limited to <30 SNPs, underlining a potential role for cgMLST in epidemiological surveillance. Finally, cgMLST allowed identification of serogroups and closely related serovars. In conclusion, the proposed cgMLST strategy allows high-resolution genotyping of Leptospira isolates across the phylogenetic breadth of the genus. The unified genomic taxonomy of Leptospira strains, available publicly at http://bigsdb.pasteur.fr/leptospira , will facilitate global harmonization of Leptospira genotyping, strain emergence follow-up and novel collaborative studies of the epidemiology and evolution of this emerging pathogen.

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“…Out of 27 retrieved strains from NCBI FTP server, 16 are observed to be pathogenic in nature, 5 are intermediate and 6 are saprophytic in nature (Table 1). Sixteen pathogenic strains of Leptospira were selected for putative drug target mining [21–22,48].…”

Section: Resultsmentioning

confidence: 99%

“…Up to 2016, global character was lacking in classification of Leptospira . Fouts et al (2016) and Caimi et al (2017) have established the classification of Leptospira by wide range inter-species genomic comparison of all known infectious and non-infectious species of the bacterium [21–22]. In the present study, we have followed the systems established by Fouts and Caimi to classify various species of Leptospira as pathogenic, intermediate and saprophytic to humans.…”

Section: Methodsmentioning

confidence: 97%

An in silico approach towards identification of novel drug targets in pathogenic species of Leptospira

et al. 2019

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Leptospirosis is one of the leading zoonotic infections worldwide. As with other infectious diseases, report of antimicrobial resistance to existing therapeutic arsenal poses challenges in the management of disease. Hence, identification of novel drug targets for the pathogen deems essential. Present study used combined approach of comparative and subtractive genomics to identify putative drug targets. Crucial genes of 16 pathogenic Leptospira strains were filtered and subjected to homology search via target identification tool “TiD”. Thereafter, comparative analysis was performed for non-homologous, essential genes to accomplish the broad-spectrum drug target. Consequently, 37 essential genes were found to be conserved in at least 10 strains of Leptospira . Further, prioritization of resultant set of genes revealed 18 were hubs in protein–protein interaction network. Sixteen putative targets among the hub genes were conserved in all strains of Leptospira . Out of sixteen, fourteen were enzymes while 8 were novel and 4 were involved in virulence mechanism. In addition, genome scale metabolic network reconstruction and choke point analysis revealed cobA (porphyrin and chlorophyll metabolism) and thiL (thiamine metabolism) as chokepoints in their respective metabolic pathways. The proposed hub genes could act as putative broad-spectrum drug targets for Leptospira species, however, these putative targets should be validated to ensure them as real one prior to utilizing them for target based lead discovery.

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Leptospira species molecular epidemiology in the genomic era

Cited by 11 publications

References 48 publications

Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics

Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics

Genus-wide Leptospira core genome multilocus sequence typing for strain taxonomy and global surveillance

An in silico approach towards identification of novel drug targets in pathogenic species of Leptospira

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