Phylogenomics of Leptospira santarosai, a prevalent pathogenic species in the Americas

Abstract

Background

Leptospirosis is a complex zoonotic disease mostly caused by a group of eight pathogenic species ( L. interrogans, L. borgpetersenii, L. kirschneri, L. mayottensis, L. noguchii, L. santarosai, L. weilii, L. alexanderi), with a wide spectrum of animal reservoirs and patient outcomes. Leptospira interrogans is considered as the leading causative agent of leptospirosis worldwide and it is the most studied species. However, the genomic features and phylogeography of other Leptospira pathogenic species remain to be determined.

Methodology/principal findings

Here we investigated the genome diversity of the main pathogenic Leptospira species based on a collection of 914 genomes from strains isolated around the world. Genome analyses revealed species-specific genome size and GC content, and an open pangenome in the pathogenic species, except for L. mayottensis. Taking advantage of a new set of genomes of L. santarosai strains isolated from patients in Costa Rica, we took a closer look at this species. L. santarosai strains are largely distributed in America, including the Caribbean islands, with over 96% of the available genomes originating from this continent. Phylogenetic analysis showed high genetic diversity within L. santarosai, and the clonal groups identified by cgMLST were strongly associated with geographical areas. Serotype identification based on serogrouping and/or analysis of the O-antigen biosynthesis gene loci further confirmed the great diversity of strains within the species.

Conclusions/significance

In conclusion, we report a comprehensive genome analysis of pathogenic Leptospira species with a focus on L. santarosai. Our study sheds new light onto the genomic diversity, evolutionary history, and epidemiology of leptospirosis in America and globally. Our findings also expand our knowledge of the genes driving O-antigen diversity. In addition, our work provides a framework for understanding the virulence and spread of L. santarosai and for improving its surveillance in both humans and animals.

Author summary

Leptospirosis is an emerging zoonosis caused by pathogenic species of a highly heterogeneous genus. Most studies have focused on Leptospira interrogans that is responsible for the majority of human infection cases worldwide. On the contrary, our knowledge is very limited for other pathogenic species, including L. santarosai, which may represent a public health problem in both humans and animals in the American continent. Our comparative genomic analyses of the pathogenic species revealed that L. santarosai is characterized by an open pangenome state with high genetic and serovar diversity. This first study of L. santarosai isolates not only contributes to the global understanding of genomics and evolution within the Leptospira pathogenic species but also provides the groundwork for better surveillance of this pathogen.