Genomic analysis of Leptospira interrogans serovar Paidjan and Dadas isolates from carrier dogs and comparative genomic analysis to detect genes under positive selection

Abstract

Background Leptospirosis is an emerging infectious disease worldwide that can cause high morbidity and mortality rates in humans and animals. The causative spirochetes have reservoirs in mammalian hosts, but there has been limited analysis of the genomes of isolates recovered from animals. The aims of this study were to characterize genomic features of two Leptospira interrogans strains recently isolated from asymptomatic dogs in Thailand (strains CUDO5 and CDUO8), and to perform comparative genome analyses with other strains. Molecular adaptive evolution in L. interrogans as signaled by positive selection also was analyzed. Results Whole genome sequence analysis revealed that strains CUDO5 and CUDO8 had genome sizes of approximately 4.9 Mbp with 35.1% GC contents. Using monoclonal antibodies, strains CUDO5 and CUDO8 were identified as serovars Paidjan and Dadas, respectively. These strains harbored genes known to be associated with acute and chronic infections. Using Single Nucleotide Polymorphisms phylogeny (SNPs) with 97 L. interrogans strains, CUDO5 and CUDO8 had closest genetic relatedness with each other. Nevertheless, the serovar determinant region ( rfb locus) showed variations in the genes encoding sugar biosynthesis. Amongst 13 representative L. interrogans strains examined for molecular adaptive evolution through positive selection under the site-model of Phylogenetic Analysis of Maximum Likelihood, genes responsible for iron acquisition ( tlyA and hbpA ), motility ( fliN2 , flgK , and flhB ) and thermal adaptation ( lpxD1 ) were under increased selective pressure. Conclusions L. interrogans serovar Paidjan strain CUDO5 and serovar Dadas strain CUDO8 had close genetic relatedness as analyzed by SNPs phylogeny. They contained genes with established roles in acute and chronic leptospirosis. The rfb locus in both serovars showed gene variation associated with sugar biosynthesis. Positive selection analysis indicated that genes encoding factors involved in motility, temperature adaptation, and iron acquisition were under strong positive selection in L. interrogans . These may be associated with adaptation in the early stages of infection. Electronic supplementary material The online version of this article (10.1186/s12864-019-5562-z) contains supplementary material, which is available to authorized users.

Comparative analysis of whole genome sequences ofLeptospiraspp. from RefSeq database provide interspecific divergence and repertoire of virulence factors

“…In fact, some virulent genes were part of the core genome of non-pathogenic clade. This result reconfirms earlier report of virulent genes in non-pathogenic Leptospira (Kurilung et al, 2019). Various known virulence factors of Leptospira were not annotated in VFDB search analysis such as Lig proteins (Lig A, B, C) , Lipoproteins (LipL32, LipL45, LipL71) (Oliveira et al, 2011), Len proteins (Len A, B, C, D, E, F) (Stevenson et al, 2007) and Tly proteins (Tly A, B, C) (Carvalho et al, 2009) etc.…”

“…Pangenome of Leptospira contains 20822 genes which is similar to the pan-genome of other genus having diverse species such as lactobacillus (Inglin et al, 2018). Earlier study has reported pan genome on species level which are generally of 7000-8000 genes (Kurilung et al, 2019). It is obvious that a genus will have larger pan-genome than its species.…”

Spatial distribution and spread potential of sixteenLeptospiraserovars in a subtropical region of Brazil

“…Our results showed considerable differences in the ecological landscape features of the distribution of each Leptospira serovar. This could be explained by the fact that different Leptospira lineages can potentially survive and adapt to different environmental conditions, as recently described by Kurilung et al (). In their study, thermal adaptation was associated with a strong positive selection for temperature in Leptospira interrogans serovars, which would be an indicator of the ability of this organism to adapt to environmental changes at serovar level.…”

“…For example, temperature and precipitation (Chadsuthi, Modchang, Lenbury, Iamsirithaworn, & Triampo, ; Desvars et al, ), high humidity and heavy rainfall (Barcellos & Sabroza, ; Goarant et al, ), as well as run‐offs, soil pH and primary productivity, have been associated with Leptospira occurrence (Fajriyah, Udiyono, & Saraswati, ; Rahayu, Sakundarno Adi, & Dian Saraswati, ; Smith, Turner, Bin, & Adam, ). In addition, a recent molecular study found strong positive selection for temperature adaptation in Leptospira interrogans at serovar level, suggesting that ecological features, such as different climatic conditions, may influence species and serovar conservation (Kurilung, Keeratipusana, Suriyaphol, Hampson, & Prapasarakul, ).…”

12 Novel Clonal Groups of Leptospira Infecting Humans in Multiple Contrasting Epidemiological Contexts in Sri Lanka

“…Whole genome sequencing and comparative genomic analysis of this collection will facilitate ongoing studies on identifying the putative virulent genes, pathogenic mechanisms with specific host adaptations, horizontal gene transfer mechanisms, and microbial resistance as shown in studies on the diversity and epidemiology of other microorganisms [64][65][66][67][68][69].…”