Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel

Leptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus Leptospira, serovars belonging to L. interrogans serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible f...

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Main Authors: Luciane A. Santos, Haritha Adhikarla, Xiting Yan, Zheng Wang, Derrick E. Fouts, Joseph M. Vinetz, Luiz C. J. Alcantara, Rudy A. Hartskeerl, Marga G. A. Goris, Mathieu Picardeau, Mitermayer G. Reis, Jeffrey P. Townsend, Hongyu Zhao, Albert I. Ko, Elsio A. Wunder
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcimb.2018.00193/full
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author Luciane A. Santos
Luciane A. Santos
Haritha Adhikarla
Xiting Yan
Zheng Wang
Derrick E. Fouts
Joseph M. Vinetz
Luiz C. J. Alcantara
Rudy A. Hartskeerl
Marga G. A. Goris
Mathieu Picardeau
Mitermayer G. Reis
Jeffrey P. Townsend
Hongyu Zhao
Albert I. Ko
Albert I. Ko
Elsio A. Wunder
Elsio A. Wunder
author_facet Luciane A. Santos
Luciane A. Santos
Haritha Adhikarla
Xiting Yan
Zheng Wang
Derrick E. Fouts
Joseph M. Vinetz
Luiz C. J. Alcantara
Rudy A. Hartskeerl
Marga G. A. Goris
Mathieu Picardeau
Mitermayer G. Reis
Jeffrey P. Townsend
Hongyu Zhao
Albert I. Ko
Albert I. Ko
Elsio A. Wunder
Elsio A. Wunder
author_sort Luciane A. Santos
collection DOAJ
description Leptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus Leptospira, serovars belonging to L. interrogans serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible for majority of the reported severe cases. Serovars Copenhageni and Icterohaemorrhagiae are major representatives of this serogroup and despite their public health relevance, little is known regarding the genetic differences between these two serovars. In this study, we analyzed the genome sequences of 67 isolates belonging to L. interrogans serovars Copenhageni and Icterohaemorrhagiae to investigate the influence of spatial and temporal variations on DNA sequence diversity. Out of the 1072 SNPs identified, 276 were in non-coding regions and 796 in coding regions. Indel analyses identified 258 indels, out of which 191 were found in coding regions and 67 in non-coding regions. Our phylogenetic analyses based on SNP dataset revealed that both serovars are closely related but showed distinct spatial clustering. However, likelihood ratio test of the indel data statistically confirmed the presence of a frameshift mutation within a homopolymeric tract of lic12008 gene (related to LPS biosynthesis) in all the L. interrogans serovar Icterohaemorrhagiae strains but not in the Copenhageni strains. Therefore, this internal indel identified can genetically distinguish L. interrogans serovar Copenhageni from serovar Icterohaemorrhagiae with high discriminatory power. To our knowledge, this is the first study to identify global sequence variations (SNPs and Indels) in L. interrogans serovars Copenhageni and Icterohaemorrhagiae.
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spelling doaj.art-bb51e38f00b2494bbac1ee900dee18602022-12-22T01:38:05ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-06-01810.3389/fcimb.2018.00193352063Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an IndelLuciane A. Santos0Luciane A. Santos1Haritha Adhikarla2Xiting Yan3Zheng Wang4Derrick E. Fouts5Joseph M. Vinetz6Luiz C. J. Alcantara7Rudy A. Hartskeerl8Marga G. A. Goris9Mathieu Picardeau10Mitermayer G. Reis11Jeffrey P. Townsend12Hongyu Zhao13Albert I. Ko14Albert I. Ko15Elsio A. Wunder16Elsio A. Wunder17Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United StatesGonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BrazilDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United StatesDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, United StatesDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, United StatesJ. Craig Venter Institute, Rockville, MD, United StatesDivision of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, United StatesGonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BrazilRoyal Tropical Institute, KIT Biomedical Research, Amsterdam, NetherlandsRoyal Tropical Institute, KIT Biomedical Research, Amsterdam, NetherlandsBiology of Spirochetes Unit, Institut Pasteur, Paris, FranceGonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BrazilDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, United StatesDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, United StatesDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United StatesGonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BrazilDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United StatesGonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, BrazilLeptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus Leptospira, serovars belonging to L. interrogans serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible for majority of the reported severe cases. Serovars Copenhageni and Icterohaemorrhagiae are major representatives of this serogroup and despite their public health relevance, little is known regarding the genetic differences between these two serovars. In this study, we analyzed the genome sequences of 67 isolates belonging to L. interrogans serovars Copenhageni and Icterohaemorrhagiae to investigate the influence of spatial and temporal variations on DNA sequence diversity. Out of the 1072 SNPs identified, 276 were in non-coding regions and 796 in coding regions. Indel analyses identified 258 indels, out of which 191 were found in coding regions and 67 in non-coding regions. Our phylogenetic analyses based on SNP dataset revealed that both serovars are closely related but showed distinct spatial clustering. However, likelihood ratio test of the indel data statistically confirmed the presence of a frameshift mutation within a homopolymeric tract of lic12008 gene (related to LPS biosynthesis) in all the L. interrogans serovar Icterohaemorrhagiae strains but not in the Copenhageni strains. Therefore, this internal indel identified can genetically distinguish L. interrogans serovar Copenhageni from serovar Icterohaemorrhagiae with high discriminatory power. To our knowledge, this is the first study to identify global sequence variations (SNPs and Indels) in L. interrogans serovars Copenhageni and Icterohaemorrhagiae.https://www.frontiersin.org/article/10.3389/fcimb.2018.00193/fullLeptospiraleptospirosisCopenhageniIcterohaemorrhagiaewhole-genome sequencingSNPs
spellingShingle Luciane A. Santos
Luciane A. Santos
Haritha Adhikarla
Xiting Yan
Zheng Wang
Derrick E. Fouts
Joseph M. Vinetz
Luiz C. J. Alcantara
Rudy A. Hartskeerl
Marga G. A. Goris
Mathieu Picardeau
Mitermayer G. Reis
Jeffrey P. Townsend
Hongyu Zhao
Albert I. Ko
Albert I. Ko
Elsio A. Wunder
Elsio A. Wunder
Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
Frontiers in Cellular and Infection Microbiology
Leptospira
leptospirosis
Copenhageni
Icterohaemorrhagiae
whole-genome sequencing
SNPs
title Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
title_full Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
title_fullStr Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
title_full_unstemmed Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
title_short Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel
title_sort genomic comparison among global isolates of l interrogans serovars copenhageni and icterohaemorrhagiae identified natural genetic variation caused by an indel
topic Leptospira
leptospirosis
Copenhageni
Icterohaemorrhagiae
whole-genome sequencing
SNPs
url https://www.frontiersin.org/article/10.3389/fcimb.2018.00193/full
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